The world number two will make his latest attempt to complete a career Grand Slam at Augusta next week and three-time Masters winner Mickelson is confident that the Northern Irishman can block out the noise as he bids to end a major drought that stretches back to 2014.
The American golfer said of the pressure on McIlroy: "That's challenging.
"But he's done it so many times in his ability to win tournaments. He's been able to compartmentalise that.
"I don't think that's going to be an issue for him."
McIlroy infamously capitulated when leading in the final round at Augusta back in 2011 but Mickelson doesn't think the star's bad memories at the tournament are preventing him from taking home the Green Jacket.
The six-time major winner said: "His ability to compartmentalise all the things that have transpired in the past is a strength of his so I don't think it'll be an issue or I don't think that's what's holding him back from winning the Masters."
Mickelson also believes that McIlroy's game is perfectly suited to the famous Augusta National course.
He said: "I think he drives the ball so long and straight that he has a huge advantage on that golf course.
"He and about 20 guys that drive it like he does will have an advantage of playing it a certain way."
McIlroy finished in the top five at the Houston Open, his final event before The Masters, last weekend and revealed that he may have some treatment on a troublesome elbow injury before the year's opening major.
The four-time major winner told the Golf Channel: "My right elbow has been bothering me a little bit so I'll maybe just get some treatment on that and make sure that is OK going into Augusta.
"I've got my coach Michael Bannon coming in, we'll do some work and make sure everything is in good shape for a week's time."