The Red Devils will reunite with the Portugal captain, who left Old Trafford for a record £80m in 2009, at the Bernabeu this week, and Neville believes that if United double up on the winger, they may keep him quiet.
"I watched him play against Sevilla on Saturday night and he scored three goals in about 30 minutes, and they were all different types of goals too," Neville told BBC Radio Five Live.
"The one way United could handle him is by getting numbers around him. I think if Ronaldo is out on the right wing against Rafael, Phil Jones might come across to cover, so they've got two men against him."
The North-West club head into the round-of-16 clash with a 12-point lead in the Premier League title race.