The Blades, who aim to become the first third-tier side to reach the last four of the famous competition since Wycombe in 2001, have ousted Aston Villa, Fulham and Nottingham Forest in the last three rounds.
They now welcome the Championship strugglers, who beat United's city rivals Wednesday to book their spot in the last eight and deny the chance of a Sheffield derby.
The Blades are on an impressive run of form having won their last eight games in all competitions, conceding only one goal along the way. Clough is keen to play down his side's chances, though admits not playing the Owls could be an advantage.
"I would disagree that we are favourites, when you are playing a team from the division above then that takes precedent as to who are favourites or not," the former Derby boss said.
"I know we are at home and have won a lot of games but I still think their Championship status makes them favourites.
"An FA Cup quarter-final, the motivation shouldn't be less, whoever we are playing, there is a semi-final at Wembley at stake whether we were playing Charlton or Sheffield Wednesday.
"I think not playing Wednesday means we are concentrating on the football, it's just an FA Cup quarter-final now, rather than a Sheffield derby."
The Blades have reached the quarter-finals the hard way, beating Colchester and Cambridge away in the early rounds, seeing off Villa and Fulham on their own patches and then coming from behind to triumph over Forest in the last 16.
Clough admits it has been tough but has urged his players to grasp the chance of becoming the first third-tier club to make the semi-finals since the new Wembley Stadium opened in 2007.
"I don't think we would have dreamed with the draw we have had that we would be in the quarter-final," he added.
"Somebody said the draw had been kind to us, but we have been away from home in the first three rounds, and then had Fulham and Forest.
"But to get to this stage as a League One club you're going to have to beat teams like that.
"I am just trying to get Sheffield United to Wembley because of what it will mean to everyone here.
"It should be in every player's mind, not to make them nervous, but they might never be this close to playing at Wembley again.
"I don't think we can win it because of the teams that are left in it, but if we get to a semi-final then anything can happen."
Harry Maguire, Jamie Murphy, John Brayford and Stephen McGinn will all be assessed.
Defender Maguire has missed the last two games due to a knee injury, while Murphy and Brayford sat out the midweek win against Peterborough with respective groin and calf problems and McGinn suffered a recurrence of a back injury in midweek.
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