Tito Vilanova takes charge of his first El Clasico in La Liga tomorrow night, with Barca eight points clear at the top of the league table thanks to a 100% record.
Di Stefano told ESPN that he believes the match is a tough one to call, but regardless of the outcome Barca have the superior side.
The 86-year-old said: "It will be a very difficult game. Both teams have players who can win them the tie.
"I hope Real Madrid win and then we can start to strike fear into the teams above us."
"But Barcelona play outstanding football, which they won't change, whether they win or lose. They are superior to everyone because they have about four or five individuals who are outstanding footballers. You can't ignore the truth."
Argentine legend Di Stefano famously made the switch to the Bernabeu despite originally agreeing a deal to sign for Barcelona at the peak of his glittering career.