Ronaldo, who spent six years with United up until his departure in 2009, has been tipped by many to be the difference between the two sides over the two legs.
Despite admitting that it will be difficult to keep the Portuguese international at bay, Rooney believes that United will have a better chance of reaching the quarter-finals of the Champions League if they manage to shackle him.
"I played with Cristiano for a number of years and he's a fantastic player, him and Lionel Messi are the two stand out players in football today," Rooney told GiveMeFootball.com.
"He's certainly the biggest threat for Real Madrid. He's an incredible talent and it will be tough to try and keep him quiet, and I'm sure if we can do that it'll give us a better chance of getting the result we want."
Ronaldo has scored 182 goals from just 179 outings for Los Blancos.