New United boss David Moyes has already remarked about having to take a few punches in his first season in charge.
Liverpool and Manchester City have landed some. But so have West Brom and Southampton, who have taken points away from Old Trafford already.
Now it is Stoke's turn.
Although the Potteries outfit have lost on their last 10 visits, not won there since 1976 and scored just four times in the Premier League this season, Hughes sees no need for fear.
"You need to be confident in your team's ability to cause an upset," said the Welshman.
"That is what I always am when I go there. The bigger the game, the bigger the challenge.
"That is what stimulated me as a player. When I don't see players stimulated by facing some of the best players in world football I question why they don't back their own ability."
Hughes has evidence his philosophy works.
In the 2005-06 campaign, his Blackburn side did a league double over their north-west rivals, one of only 13 occasions United have suffered the experience in the entire Premier League era.
The problem for many teams is a feeling of defeat from the moment they emerge from the dressing room.
"Even when I was playing for Manchester United you thought you had teams beaten in the tunnel," said Hughes.
"That is what Old Trafford can do to teams and players."
But with Sir Alex Ferguson no longer around, the intimidation factor does not seem quite as strong.
"He has driven the club and the determination of the group of players he had at any given time for the last 25 years," said Hughes.
"It was a huge challenge to go there and beat his team.
"He is not there now but I'm sure that over a decent period David will take that over and create teams of his own that will have a similar impression on opposition teams."
There is another area where Ferguson's absence might be having an impact.
For without his brooding presence in the background it is possible referees do not feel quite as on edge either.
"I have to be careful talking about referees before games but yes it's difficult to get key decisions because there are 75,000 spectators there," said Hughes.
"It's a huge club and if mistakes are made in officiating key moments it gets highlighted.
"Its not questioning the integrity of the officials, it's just human nature."
This is the mega club Moyes took on when he answered that infamous telephone call from Ferguson in April, telling him he was to be the Scot's successor.
There was a time when Hughes was talked about as a potential candidate for the role, although he probably killed that idea when he accepted the Manchester City job.
"It is a huge and fantastic job," said Hughes.
"No one is going to turn down the opportunity when offered it, but it is a difficult job because of the stature of the club and huge demands surrounding it every single day.
"That is why Sir Alex's tenure was so great.
"He was able to do it for 26 years, which is quite astounding given the demands on managers today.
"But to pay David his dues, he's been successful over a long period at Everton. He is the right appointment."