If United win the cup this year it will be the first time in 12 years and boss Louis van Gaal has admitted his job could be on the line if United lose.
"When you lose it is more worse and I predicted already, before the game against Southampton, that I cannot lose any more because I am then condemned for the fourth time that I have been sacked. Maybe then you have written the truth, because sometimes it happens." he said at Thursday's press conference.
The game marks another milestone as it will be United's 49th televised FA Cup tie in a row. The last time they played a tie which wasn't shown live was in the 2003/4 season. It means that smaller clubs are less likely to see some of the TV cash which runs into six figures at this stage.
The match with Derby is live on BBC1 at 7.55.