"Certainly we go in as underdogs," Fulham manager Roy Hodgson told reporters on Friday. "We're realistic but ... if we did want to take solace from the fact this can be done, we've got Portsmouth last year.
"In the Cup everything is possible."
United, still on course to win six trophies this season, are likely to include FIFA World Player of the Year Cristiano Ronaldo in attack.
"Ronaldo is a player I respect enormously," said Hodgson. "He's got wonderful ability and if we're going to keep him quiet, which is a very difficult thing to do, we'll have to be very good."
Hodgson side-stepped Arsenal manager Arsene Wenger's comments that Ronaldo's "arrogance" can sometimes make him the target of bad tackles.
"He (Ronaldo) has got a lot of confidence," he said. "Someone who is very confident in his play would always run the risk of being called arrogant."
RASH CHALLENGE
Hodgson added his players would have to be careful not to give away a penalty by making a rash challenge.
"(Ronaldo) goes at such speed that when he loses control of the ball and people are in there making attempted challenges, the referee has a difficult task," he said.
United manager Alex Ferguson, who has already won the Community Shield, Club World Cup and League Cup this season and is also chasing success in the Premier League and Champions League, said mid-table Fulham would be tricky opponents.
"Their home record is good and we're in for a tough game," said the Scot.
