Sir Alex's side face the Liga champions at the Santiago Bernabeu, with the match representing the first time former United man Ronaldo has played against the club with whom he made his name.
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Speaking to MUTV, Ferguson said: "The responsibility will be with Rafael. Rafael's maturity this season has been fantastic.
"Obviously Robin van Persie has been sensational but, outside that, Rafa and Michael Carrick are having their best seasons ever.
"He's Brazilian so he doesn't fear a thing. I trust him and have faith in him tonight."
Since selling Ronaldo for £80 million, Sir Alex believes the Portugal international has developed even further but adds that if any team know how to stop him, it is United.
"He's flourished since he's come to Madrid," the 71-year-old said. "You'd have to be stupid not to respect his goalscoring record. But if one team knows about Ronaldo it's us.
"We had him for six years so we know everything he can do on a football pitch. We probably have an advantage in that respect, when it comes to facing Ronaldo."