La Liga's top two meet at the Santiago Bernabeu in what could be a decisive fixture in this season's title race.
Madrid hold a three-point lead over the champions, with a game in hand, and former Bernabeu captain Casillas feels Madrid deserve to be crowned champions for their performances this season, while warning Barca that a defeat could end the defence of their crown.
"As a one-off game, it'll do a lot more damage to Barcelona," he told Movistar+.
"I want Madrid to win and secure La Liga that little bit more. They deserve it."
There has been speculation that the 35-year-old could earn a recall to the Spain squad, with head coach Julen Lopetegui admitting last month that "the doors are open" to La Roja's record appearance-maker.
"I haven't given up on the national team and I'm not going to," said Casillas, who has 167 caps for his country. "The day that it happens, I'll be the one to say it."