The 55-year-old, who was recalled to the post after his successor Alberto Malesani was dismissed at the end of February, survived just two games in his latest spell with the club
The former Inter boss was re-appointed as the Serie A bottom club's boss at the end of last month, replacing Alberto Malesani, who himself had only been at the helm for 19 days.
However, following a 0-0 draw with Torino and a 2-1 defeat to Siena on Sunday, club president Maurizio Zamparini has decided once more to part ways with the 55-year-old.
"After a meeting between the board of directors, Giorgio Perinetti and Gian Piero Gasperini, Palermo announces that an agreement has been reached with the coach for the consensual termination of his contract," a statement read.
Gasperini's previous spell at the club only ended on February 4, before Malesani was placed in charge for less than three weeks.
Early reports in Italy suggest Giuseppe Sannino, who was sacked by Zamparini in September last year, could be recalled to replace Gasperini at the helm. He would become the 27th coaching appointment at the club since 2002.
Earlier on Monday, Zamparini launched a tirade against his players following their defeat to fellow strugglers Siena.
"We cannot do anything to attain salvation, I think it's crazy just to think that. We need a lot of luck, and my players have not proven themselves to be real men on the pitch this year," he told Itasportpress.
"In the 30 years I've been in football, I have only been relegated twice with Venezia, and twice we came back to Serie A. I will only be resigned [to relegation] through mathematics, but the current situation is really bad."