Captain Honeyman underwent an ankle operation in the summer and made his return from the bench in the home game with Sheffield United last month, but picked up a separate groin issue.
Huddlestone has also been sidelined for the past month with a hamstring problem sustained in the build-up to the Blades encounter on September 18.
On whether key pairing Honeyman and Huddlestone could be involved from the off at the John Smith's Stadium, McCann said: "They could start.
"When they come back into training with us, they are ready to go. We have also got to mindful of how long they have been out for. We have got to be mindful with George as his last start was six months ago if you put that into context.
"But George is that type of character who if he started the game on Saturday, there would be no difference as it is just the way he is.
"Tom has been out for about four weeks with a little grumbling hamstring, so it is nice to have both of them back and it strengthens the competition and with Matt Smith coming back from Wales, the midfield is looking strong.
"It is a nice headache to have as a coaching staff."
McCann has a 20-strong squad to pick from ahead of the game against the Terriers, but will be without Alfie Jones until late autumn.
The Hull chief added: "It is not good news with Alfie. He has done his hamstring and will be three or four weeks (out), maybe longer. But what it does is it gives Alfie an opportunity.
"I have mentioned before about players coming back and we had the issues with Covid and stuff at the start of the season and it just seems that all those players who contracted that virus started to pick up niggles and knocks and Brandon Fleming is another one who will be out for a bit. It is a knock-on effect that Covid has to people's muscles and it has not been great for us really.
"It gives Alfie a chance to work hard in the gym and there is a lot of stuff we can do with Alfie and Brandon to keep their fitness levels high.