On Tuesday night, the 26-year-old helped his side set up the mouth-watering tie with their west London rivals by defeating then MK Dons 1-0 in their third-round replay.
The Hoops won the league clash between the sides at Loftus Road, but the match is remembered for allegations that John Terry aimed racial abuse at Ferdinand. Terry has always denied the allegations.
Asked whether he had any concerns about playing Ferdinand against Chelsea, Hughes said: "No.
"Obviously I will speak with all the players leading into the game and get an understanding of where they are in their mind in terms of the mentality that you need to go into that game.
"It is a challenging game and a big test for us, but knowing Anton and having seen him over the years I am quite sure he will want to be involved in that game.
"It is a big game anyway because of the opposition and they are near neighbours.
"We will take it when it presents itself but our focus is very much on the weekend against Wigan.
"It is a huge game for us and we need to improve on what we have improved today and arguably we have to be better than what we were on Sunday as well to win the game.
"There is a big challenge ahead of us but we are ready for it. It is an exciting time for the club and I am happy to be here.
"Everybody is working towards the same end."
Hughes is unsure whether any new transfer business will be done ahead of this weekend, with deals for Chelsea defender Alex and Sao Paulo's Henrique in the pipeline.
The Welshman will be hoping for a much improved performance against Wigan after seeing his side outplayed by MK Dons for most of Tuesday night's match, where Danny Gabbidon's second-half header proved the difference.
"It was very important," he said. "I think in terms of our performance we did not get anywhere near what we produced against Newcastle.
"It is a little bit unfair considering we playing on Sunday then Tuesday and that showed in our sharpness, or rather lack of sharpness.
"Credit to MK Dons, they were full of running and passed the ball really crisply and moved us around the pitch.
"It was a hard night but we stuck at it and if I have taken anything from the two games I have taken charge of, is the attitude.
"They dig in, try to work hard and try and get something from the game and that is what they did tonight.
"It is the first time we have progressed in the competition for many years and that was the prize on offer.
"That is what we were after, but we understand performance-wise we can do better.
"At the weekend we will be better prepared with more preparation time and I am sure our performance levels will be better than what we were able to produce tonight."
QPR can welcome back skipper Joey Barton after suspension this weekend. The midfielder watched Tuesday night's game and spoke to MK Dons manager Karl Robinson after the match.
"I spoke with Joey downstairs and he was full of praise for the group of players we have got and so was their staff," Robinson said.
"They showed great respect for us and an awful lot of class in the way they got the victory in the end and the way they conducted themselves.
"I think sometimes that goes unnoticed. Footballers get an awful lot of stick at the highest levels for being arrogant, but fair play for their conduct today.
"It will mean a lot to my players, their kind words, and we will take great pride and belief from it."