Midfielder Paul Pogba is set to make his full debut for United.
Fellow youngsters Ezekiel Fryers, Ravel Morrison, Michael Keane and Ben Amos have all been involved in United's run to the last eight and will hope to be handed another chance to impress manager Sir Alex Ferguson.
United will also have plenty of first-team experience at their disposal, including Brazilian full-back Rafael who is in line to make his first appearance of the season after a shoulder injury.
Crystal Palace boss Dougie Freedman faces a selection quandary.
The tie at Old Trafford will be the first of two matches in the space of 48 hours for the London club, who host Derby in the Championship on Friday night.
Freedman admits there is no way he can play the same side with the games so close together, and the Scot expects to fully utilise his squad.
"We've got to take into account that 48 hours later we are playing Derby live on the television, so we've got to make sure we are also prepared for the quick turnaround," said Freedman. "I will be very shocked if 20 players don't get some game-time over the next two matches. I will be mixing both teams around to give me the best opportunity to win both games.
"There will be an opportunity for some players who haven't played so many games to play in one of these games. I will be picking a team that I believe can hold on for as long as possible against Manchester United and then pick a team that can hopefully beat Derby."
The likes of goalkeeper Lewis Price, defender David Wright, midfielders Jonathan Parr, Darren Ambrose and Kagisho Dikgacoi and strikers Jermaine Easter and Steffen Iversen are available for recalls.
Manchester United (from): De Gea, Lindegaard, Amos, Thorpe, Rafael, Smalling, Fabio, Jones, Evans, Evra, Fryers, Nani, Valencia, Gibson, Carrick, Fletcher, Pogba, M Keane, Morrison, Cole, Vermijl, Park, Young, Rooney, Hernandez, Berbatov, Diouf, Macheda.