Rooney has not scored at Anfield in 10 years, with his only goal in 10 appearances on Merseyside coming in January 2005 when United won 1-0.
The 29-year-old England international returns to Anfield on Sunday as United look to cement their spot in the Premier League's top four and Van Gaal has backed his captain to end the goalscoring drought.
"I don't think that Wayne has a [mental] block, he's a very experienced player," Van Gaal said.
"He has played on all the grounds in the world, so I don't think that he shall be influenced by the fans at the stadium, or something like that.
"It's strange but it can be like this, and I hope I can change it with Wayne."
Rooney is not alone in his struggles at Anfield, with United having only won one of their past seven visits to Merseyside.
"I have always my assistant manager [Ryan Giggs] to say that to me," Van Gaal added.
"He said that also to the players, in his presentation of the analysis of Liverpool, but I also have the cook, Mike (Donnelly), and he is saying that every day to the players and to me!
"I like that, because that shows that it is a very particular match, especially for the fans of Manchester United, and it helps also to focus and concentrate on this match."
Get the best features, fun and footballing frolics straight to your inbox every week.
Thank you for signing up to Four Four Two. You will receive a verification email shortly.
There was a problem. Please refresh the page and try again.