The blue Ford Fiesta was on the B6265, travelling from Pateley Bridge in the direction of Ripon, when it came off the road at around 2.30pm yesterday.
It then collided with a tree, close to the G&T's Ice Cream Parlour at Home Farm.
A North Yorkshire Police spokesman today said that all four occupants had been taken to hospital following the crash.
He said: "A 28-year-old man was taken by air ambulance to Leeds General Infirmary with serious abdominal injuries and the other three occupants were taken to Harrogate District Hospital. Two remain in a serious condition."
Those travelling in the car were two men and two women, who are all from the Cleveland area and are aged between 28 and 36.
The road was closed until 6.30pm to allow police to conduct a thorough investigation of the scene
Now anyone who saw the blue Ford Fiesta prior to the crash or any witnesses to the collision, including anyone who stopped to help, is being asked to contact police.
Email [email protected] or phone 101, select option 2 and ask to speak to TC Steve James, quoting reference 12170153846.
The independent crime charity Crimestoppers can be contacted anonymously on 0800 555 111.