The task of taking on Jose Mourinho's men away has been notoriously difficult, with the London outfit suffering only one home defeat this season and none in the Premier League at all in either of the Portuguese's spells in charge.
They did, however, suffer a dramatic 3-2 league loss at Stoke last month - something Hughes is optimistic may count in his team's favour with regard to psychology this weekend.
The Welshman, a former Chelsea player, said: "We take confidence from the fact that we have already beaten them this season.
"It wasn't at Stamford Bridge and, historically, Stamford Bridge when Chelsea are under Mourinho has been a very difficult place to get a positive result.
"But the fact that we have beaten them I think will help us - and possibly play on their minds somewhat.
"We have to try to use that to our advantage.
"There won't be any apprehension in terms of what we are going to try to do.
"If we do it well, on our day we are difficult for anyone, as we have proved - and as Chelsea know."
After the Chelsea game, Stoke - currently 14th in the Premier League and only four points clear of the relegation zone - have a top-flight fixture at Sunderland on Wednesday.
Hughes admits he will be mindful of the trip to the Stadium of Light when he makes his team selection for Sunday's match, but has also stressed he feels it is possible for him to "go strong" for the cup tie and that it is a case of "getting the balance right".
When it was put to him that Stoke fans might deem the Sunderland encounter more important than the Chelsea one, Hughes said: "I can understand that.
"I think Premier League points are vitally important to us.
"But we are playing Sunday and then Wednesday and I feel, if I want to go strong, I can do because of the time-scale involved - obviously it would have been different if we had been playing Sunday and then Tuesday.
"The extra day gives us time to recover, so we will see.
"I think there is an opportunity to go as strong as I would like, but it is about getting the balance right as well and I am mindful of the game on Wednesday."
Stoke goalkeeper Asmir Begovic could make his return to action on Sunday after being sidelined for six matches by a broken finger.
John Guidetti, the frontman on loan from Manchester City, will be assessed having felt ill on Friday, while Robert Huth (knee), Andy Wilkinson (heel) and Matthew Etherington (calf) remain unavailable.
Winger Jermaine Pennant will not feature as he has been released by the Potters.
Meanwhile, Stoke have reached an agreement with Cardiff over a move for Peter Odemwingie, which will see Kenwyne Jones head to south Wales in a player-exchange transfer.
The Potters have announced that the deal is subject to both strikers passing medicals and agreeing personal terms - but they hope to conclude their move for Odemwingie over the weekend.
The Nigeria international only joined Cardiff in September, moving from West Brom for a fee believed to be in excess of £2million.
The 32-year-old signed a two-year contract and netted twice in his first four games for the Bluebirds - however, he has failed to add to that tally in 13 appearances since.
Jones, a Trinidad and Tobago international once of Southampton and Sunderland, has fared better.
The 29-year-old has netted five goals in 10 games. However, none of them have come in the Barclays Premier League, with four in the Capital One Cup and the other in the FA Cup defeat of Leicester earlier this month.
Speaking after his side's 1-0 FA Cup fourth-round victory at Bolton, Cardiff boss Ole Gunnar Solskjaer said: "There is potentially a deal to be done, with Peter going to Stoke and Kenwyne coming to us.
"Obviously, you cannot confirm anything until papers are signed and medicals are done, but we are quite a long way down that road.
"I can't say anything about any other players, but I know Stoke have brought out a statement so I can confirm what they have said."
Jones sent a text message to Hughes the night before Stoke's 5-3 home league defeat to Liverpool on January 12 saying to say he was not available to play in the fixture.
That resulted in the player being fined two weeks wages and not being considered for selection by Hughes for the next match, a 1-0 league loss at Crystal Palace.
The manager had said on Friday that Jones was in his thinking again for Sunday's FA Cup trip to Chelsea, but it would now appear likely he will not play another match for the Potters.