Juric, fired twice by the club last year, was dismissed again after Genoa were knocked out of the Coppa Italia on Thursday by third tier side Virtus Entella on penalties following a 3-3 draw.
"Genoa Cricket and Football Club announces that it has entrusted the technical leadership of the team to former Italy coach Cesare Prandelli," the club said in a statement.
Genoa, founded in 1893 and Italy's oldest active club, are 14th in Serie A with 15 points from 14 games and only four clear of the drop zone. Their next game is at home to SPAL, who are one point below them, on Sunday.
Juric was recalled in October to replace Davide Ballardini but failed to win any of his eight competitive matches in charge.
The 43-year-old was first appointed by Genoa before the start of the 2016/17 season. He was sacked in February 2017, to make way for Andrea Mandorlini, but re-hired two months later after Mandorlini was himself dismissed.
Juric was again sacked in November 2017 when Ballardini -- who himself has coached the team three times -- was hired.
"The club sends an affectionate greeting and heartfelt thanks to Ivan Juric for the dedication he has given in this experience," said the club.
Since then, he has had short stints with Galatasaray and Valencia and in the United Arab Emirates with Al Nasr.
Of the six coaching changes in Serie A this year, two each have been at Chievo and Genoa with one apiece at Empoli and Udinese.
(Writing by Brian Homewood Editing by Toby Davis)
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