"I have never before publicly commented on situations that are so complex and involve such diverse emotions, but this situation we are experiencing is exceptional," the 33- year-old midfielder wrote in a Facebook message yesterday.
"One thing I know for sure: before we do any more harm, those who are responsible for all this must hold dialogue. Do it for all of us. We deserve to live in peace."
Iniesta was the hero of Spain's 2010 World Cup final victory over the Netherlands, scoring his side's dramatic late goal in a 1-0 win after extra time.
Tensions mounted between Catalonia and Madrid this week after Catalans went ahead with a banned independence referendum last Sunday that was marred by police violence.
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The government has refused calls for mediation in the dispute and Catalan leaders have threatened to declare independence in days.
The football club, one of the biggest in the world and a strong symbol of Catalan identity, called for "dialogue and respect" in a separate statement.
"FC Barcelona, as one of the country's best-known entities, demands that a process of dialogue and negotiation be launched to find political solutions to the situation Catalonia is experiencing," it said.
Iniesta's Barcelona teammate Gerard Pique, a Catalan native and another Spain World Cup hero, was jeered by fans at training this week for supporting the independence referendum.
He insisted he would keep playing for Spain until he retires from international football after next year's World Cup.
Spain captain Sergio Ramos on Thursday risked creating tensions with his national teammates over Catalonia when he praised the Spanish king's TV address over the crisis.
King Felipe VI's speech Tuesday dismayed many Catalans as he described the separatist ambitions as "illegal" and made no mention of those hurt in police violence when they tried to vote in the banned weekend referendum.
"I take my hat off to him," Ramos said at a press conference on the eve of his country's World Cup qualifier against Albania.
Ramos suggested last week Pique should keep his opinions to himself if he did not want to be booed, but on Thursday he insisted that the Catalonia crisis had not eroded team spirit in the national camp.
"We have an excellent relationship despite our different characters and different ways of thinking," Ramos said.