The west Londoners have already seen off Faroese minnows NSI Runavik in this year's competition and now head to Belfast hoping for a similarly smooth ride at Seaview.
However, Northern Ireland international Hughes insists everybody at Fulham is wary of the threat Crusaders pose and will make the most of playing in his homeland.
"I have played here [at Seaview] once before when I was about 13 or 14 years of age at schoolboy level," he told fulhamfc.com.
"It's good to come back and it's a competitive game, which is good for everyone.
"I've been part of teams when you're the underdog so I know the mindset in these games - flip that around and we're well aware of what the Crusaders want to do.
"Hopefully it will be another step for us along another long road in Europe.
"The one thing about our club is we're well prepared and we never take any team for granted, whether it's a pre-season game or the Europa League final.
"We treat every game in the same manner. Our scouts have been down here [to watch the Crusaders] a couple of times and we've been well briefed.
"I think that's why we've had the success we've had over the past couple of years - we're well prepared and we've got a good bunch of lads that take it all on board. We've always remained very grounded."
Former Liverpool left-back John Arne Riise will not feature for Martin Jol's side after completing his move to Craven Cottage yesterday, while Crusaders will be without skipper Colin Coates through injury.
Chris Morrow has also been ruled out of the clash but Paul Leeman is set to make his competitive debut for the IFA Premiership part-timers.