Hull face the League One club in the last four at Wembley on Sunday and will be aiming to reach the final of the FA Cup for the first time in their history.
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Strikers Nikica Jelavic and Shane Long are both ineligible for the clash, affording manager Bruce the option to hand other attacking players the chance to shine.
But the former Sunderland, Wigan Athletic and Birmingham City boss knows that some players will have to be left out.
"It's a semi-final and I'm going to disappoint some people. Everyone wants to play and rightfully so, it's Wembley," Bruce told The Hull Daily Mail.
"That's when your job becomes horrible and nasty because you've got to let people down.
"I've got 25 players and I can pick 11, so I'm going to have more people disappointed than happy.
"George Boyd, for example, has made a huge contribution and he has a great chance but it's not easy."
Premier League Hull are heavy favourites to progress to the final, but Bruce - who won the FA Cup three times with Manchester United as a player - is taking nothing for granted ahead of the meeting with Nigel Clough's side.
"You look at what Sheffield United have done and nothing's a given at Wembley," he added.
"I remember my first one [with Manchester United in 1990] when we were supposed to trounce Oldham [Athletic] and we got away with a 3-3 draw.
"A semi-final is a semi-final. There's nerves, edginess, you need a bit of luck and the bounce of the ball.
"We may never get a better chance of getting to an FA Cup final, but Sheffield United will be thinking exactly the same thing.
"We've got to perform on the day and that's the key. No matter what division you're in, you have to perform on the day."