The Cottagers face a daunting trip to face the Premier League champions, who are looking to reclaim top spot from neighbours Manchester City.
Sir Alex Ferguson’s side thrashed the Londoners 5-0 at Craven Cottage in December and will be confident of extending their winning run to six games.
Fulham have also only ever won once in the Premier League away to the Red Devils and head into the match on the back of a 3-0 home defeat by Swansea last weekend.
"You need a lot of belief in yourself to win there," he said.
"Look at Crystal Palace in the cup, they did ever so well. My old team Ajax beat them and Blackburn have beaten them so that is the feeling you need.
"You need to feel you're in with a chance otherwise you may as well stay here in London.
"Maybe it is [the biggest challenge in the Premier League] now because they are top of the league, but I can imagine over the last couple of years Chelsea were probably the number one in England.
"Then Man United won the league so it varies, but it is a big game.
"It is one of the biggest games for a club like Fulham, but even when you go to Chelsea or even Arsenal they are probably the same."
Jol could come up against two of his former players in Monday’s fixture, with Dimitar Berbatov and Michael Carrick, who played under him at Tottenham, possibly set to feature.
"I think Berbatov has done at United what he did for Spurs, which is score goals," he said.
"Of course it is at a different level, but overall he has done well even though it is difficult for him to get a regular spot in the team.
"For Carrick it is different. He was one of the last youngsters at West Ham and we got him for not a lot of money and he never looked back.
"He was always playing for me, went for big money to United and was a regular and won all the prizes. That is what he wanted and he did it."