A hero to Real fans and club captain for more than a decade, Casillas has barely featured since recovering from a broken hand, with Mourinho preferring to stick with Diego Lopez, who was brought in as cover from Sevilla in January.
Mourinho has hinted he may leave at the end of the season and he appeared to confirm reports his relationship with Casillas had broken down with a series of barbed comments in a news conference on Friday.
He said he regretted not buying Lopez earlier in his three-year stint in the Spanish capital and that he could not work with players who "think they are above the rest".
Fans at the Bernabeu on Saturday made their feelings clear when Casillas's name was roundly cheered when it was read out among the list of substitutes, while Mourinho was whistled by a significant section of the crowd.
The sense that all is not well at the club following Tuesday's elimination from the Champions League was heightened after the game when Pepe, Mourinho's Portuguese compatriot, criticised the coach in a television interview.
Pepe's comments were particularly surprising given that he and Mourinho share the same agent.
"In my opinion, maybe the coach's words (on Friday) were not entirely appropriate," he told broadcaster Canal Plus.
"We have to show a bit more respect for Iker," he added.
"Iker is a player who is part of Madrid, he is an institution. In this club and in Spain. He has to know that we the players are with him."
As has become customary when Real win a league match, Mourinho sent out his assistant Aitor Karanka to give the post-match news conference on Saturday.
Asked about the fans' reaction to Mourinho, Karanka said it had to be respected.
He declined to comment on why Mourinho had unusually elected not to emerge from the dugout during the match.
With Barcelona closing in on the La Liga title and their reign as champions all-but over, Real still have one more shot at silverware this season in the King's Cup final against Atletico Madrid on May 17.
"We have a Cup final and we want to give the title to our fans and I believe all the players are important right now," Pepe said. "We shouldn't put anyone down, least of all Iker." — Reuters