LaLiga president Javier Tebas claims Gianni Infantino is "destroying the very essence" of football and believes his time as FIFA president has come to an end.
Infantino has faced criticism following his failed plan to to seek private investment in a company which would run FIFA's competitions and sell stakes in the World Cup to private investors.
FIFA then revealed it "will not proceed" with plans and Infantino on Wednesday apologised to national associations over how the plan was developed.
Associations such as UEFA and the Football Association have called for Infantino to resign.
The pressure notched higher this week when UEFA confirmed a "departure payment" was made to a female employee who is alleged to have been in a relationship with Infantino while he was general secretary of the organisation -- Infantino denied the claims.
Tebas, who has been president of LaLiga since 2013, is the latest person to call for the FIFA president to resign and thinks his position has now become untenable.
Speaking to Le Monde, he said: "For me, Gianni Infantino's time has long since passed.
"I'm not saying this because of recent events; I have noticed this style of management for a long time, though everyone else seems to be discovering it only now.
"Gianni Infantino is not someone who contributes to the growth of football. On the contrary, his projects are destroying the very essence of the sport: the national leagues.
"Football is not limited to the elite. For me, the Infantino era is over.
"What remains to be seen is when that will take effect and how the succession will unfold. I hope it is not just a matter of swapping out some people for others, but of a genuine overhaul."
- UEFA stands by World Cup boycott plans despite FIFA, Gianni Infantino apology
- Norway calls on Infantino to quit amid backing from Mexico, Argentina
FIFA hit out at Infantino's critics and accused them of trying weaken his authority so he is removed from his role without a due re-election process while the Mexico and Argentina associations have come out in support of him.
A European threat to boycott the World Cup remains in place despite Infantino's apology, with Tebas adding: "What is happening does not surprise me.
"What does surprise me is the reaction of many people who remained silent for years.
"This episode is only the tip of the iceberg of what has been going on within an institution, FIFA, but also more broadly in football, where there are no real governance policies. And the problem is not limited to one person; it is about an entire system.
"The old system can persist even when the people change. Let's hope things truly change, that a new leader arrives, and that new governance is established at FIFA."
