Carmen Aristegui had been publicly feuding with her employer, MVS Radio, in recent days after two of her investigative reporters were fired by the company.
She complained about the dismissals on the air Friday, demanding that her colleagues be reinstated and lamenting about an "authoritarian wind" in the country.
MVS said the two journalists had been fired for using the company's name without permission in their participation in MexicoLeaks, a website created by civic groups and other media outlets to receive leaked documents showing acts of corruption.
In a statement, MVS said it could not allow one of its collaborators to "impose conditions and ultimatums on the administration."
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Aristegui's investigative team revealed last year that President Enrique Pena Nieto's wife, former soap opera star Angelica Rivera, had bought a Mexico City mansion from a government contractor.
The story sparked allegations of conflict of interest, which the president denied, adding more headaches to Pena Nieto as he faced protests over the presumed massacre of 43 missing college students.
Her supporters voiced their discontent on social media, with the hashtag #InDefenseOfAristegui2 (#EndefensadeAristegui2) a top trending topic on Twitter in Mexico.
"Carmen Aristegui is an essential voice in our public life. Her departure from MVS seriously damages freedom of speech in Mexico," leading historian Enrique Krauze wrote on Twitter.
The radio station's website was briefly hacked on Saturday, with a message apologizing for the firing of Aristegui's two journalists.