Police declared a major incident after the blasts at Wood Flour Mills in the village of Bosley, near Macclesfield, Cheshire.
Fire crews said the incident involved the collapse of a four-storey building and warned there was a risk of further explosions.
“There is a fully developed fire in several areas,” a Cheshire Fire and Rescue spokesman said.
“Firefighters are facing a dangerous situation as they cannot rule out further explosions. People are advised to avoid the area.
“It is believed at this stage that four people are trapped.”
A 29-year-old woman suffered serious burns and blast injuries to her head, face, arms and chest, West Midlands Ambulance Service said.
She has been airlifted to Queen Elizabeth Hospital Birmingham for further specialist treatment, while two other people who suffered burns have also been taken to hospital.
One person was flown by air ambulance to Wythenshawe Hospital in Manchester, with the other taken to Royal Stoke University Hospital, the North West Ambulance Service said.
A further 35 people have also been assessed at the scene by ambulance staff but were not injured.
The explosions at the wood treatment works shook nearby homes and emergency services have warned local residents to close windows and doors because of smoke in the area.
Emergency crews were initially called to reports of an explosion at the site at around 9.10am. Cheshire Police confirmed later there had been a further two blasts.
Student Charli Alston, 18, who heard the first explosion as she walked her dog, said: “I was walking down my drive and there was just a huge bang. It sounded like a thunder cloud, we didn’t know what it was because it was sunny then.
“We looked over and there were massive plumes of flames. Almost as high as the hill next to it.
“I couldn’t tell you how high the flames were, but I’d say a good 70 metres into the air. Huge. The sound was really really loud and there was loads of billowing black smoke.
“We phoned 999 straight away, because it was pretty terrifying watching it.”
Charlotte Maher, who lives close to the scene of the explosions, said the incident was a “major devastation” for the village.
She told Sky News: “The house completely shook. We thought it was an earthquake.
“Black smoke started coming out and we heard the sirens.
“Because Bosley is such a small village, a lot of people we know work there.
“It’s a major devastation for the village.
“We felt two vibrations here five minutes down the road. I can’t imagine how the houses down there took it.”
Fifteen fire engines have been dealing with the aftermath of the explosions, Cheshire Fire and Rescue said
A spokesman for North West Ambulance Service NHS Trust said: “Our primary role is to assess the level and nature of injuries, and ensure that those people most in need are treated first and taken to hospital.
“At this stage, it is too early for us to confirm the number of casualties.”
More than 40 pupils at Bosley Primary School, which is about a mile away from the explosion site, were being kept inside the school building with the doors and windows closed.
The school is due to close for the summer holidays today, a spokesman said.
The incident in Cheshire comes after two men were killed in an explosion at an industrial unit in Norfolk on Monday.
Daniel Timbers, 29, and Barry Joy, 56, both died in the blast at digger bucket manufacturer Harford Attachments in Norwich, which is believed to have been caused by a fireball resulting from a build-up of toxic fumes.
Cheshire Fire and Rescue said 20 people were working at the site at the time of the explosion and there were “quite a few walking wounded”.
Chief fire officer Paul Hancock said: “We are still dealing with four unaccounted people. We believe they are somewhere in the building. We will endeavour to deal with that issue in a few hours time once we get the incident under full control.
“There are a significant number of hazards that are presenting themselves to us as we deal with the incident.”
Group manager Steve Barnes, from Cheshire Fire and Rescue Service, said: “A large factory has collapsed to a single level pretty much. It is quite a scene of devastation to be honest.
“A few cottages alongside were affected by the blast. We’re unsure what the blast was caused by as yet.”
Patrick Jones he was “absolutely gutted” to hear about the explosion after he clocked off his shift at 6am at the affected business, Wood Treatment Ltd.
He said: “I am still worried about my mates. There are four of them that are still missing.
“I was on shift until six o’clock and the changeover for people coming on is at eight o’clock.
“I have tried to get down there to see if I can get but they won’t let anybody through.”
He said his employers were “brilliant” and added: “You couldn’t ask for a better place to work.
“As long as my mates get out, that is all I am bothered about.”
Mr Hancock said that between 70 and 80 firefighters were at the scene, together with police officers and ambulance crews.
Colleagues from Derbyshire, Staffordshire and Greater Manchester were assisting, along with Merseyside firefighters who are part of an Urban Search and Rescue Team.
He said: “The crews have worked exceptionally hard in very, very difficult and challenging circumstances with a number of hazards.
“We are in a place now where we are dealing with the fire. We have secured the scene.
“We are still working on the assumption that four people are unaccounted for.”
He said it was too soon to speculate on the cause of the blaze.
“We are still in what we call an acute phase,” he said. “One of our main concerns now is that the site of the incident is safe to commit crews to do a fire investigation and potential searches.”
Mr Hancock said the last explosion at the site happened at about 10.15am.
Cheshire Police said 35 people have been “directly affected” by the incident.
Four were treated at the scene for breathing difficulties and a further four have been taken to hospital for treatment - one in a serious condition.
There have been three explosions and four people remain unaccounted for, police added.
A safety cordon has been set up around the scene.
Chief Inspector Paul Carroll said: “We continue to work with all our emergency service partners and the local authority to deal with this incident. At this time we believe four people are trapped and we’re dealing with multiple explosions.
“I would advise anyone in the area to ensure they keep their windows and doors shut, and any drivers in the vicinity should switch off their air conditioning. Please avoid the area while we deal with this.”
Three men and one woman are said to be unaccounted for.
A constant plume of smoke continues to emanate from the site.
Speaking in Bosley, the leader of Cheshire East Council, Councillor Michael Jones, said: “Our prayers and hopes are that these missing people will be found alive and well but with the building collapsed we are obviously concerned.
“This has had a major impact on such a very special village. It’s a small community and there were 50 jobs there.”
David Rutley, Conservative MP for Macclesfield, said: “I have met some of the people who were then when the blast took place. They are clearly in a state of shock.
“It is a huge shock to the community, it’s a close-knit community.
“It’s absolutely vital they get all the support they need.
“It is entirely appropriate we have seen a fantastic response from the emergency services and the council.”
The council have set up a helpline for residents of Bosley and those affected by the incident.
The number is 0300 1235034.