De Zerbi became the latest in a long line of coaches at the Sicilian club when he replaced Davide Ballardini two games into the current campaign.
But his reign, too, has ended in disaster.
Palermo registered a club record seventh consecutive defeat when they lost 1-0 at home to Lazio at the weekend.
And trigger-happy club president Maurizio Zamparini finally snapped when they lost 5-4 on penalties to second division side La Spezia in the fourth round of the Cup on Wednesday.
La Spezia have set up a plum last 16 tie with Napoli, while Palermo will look to save their season by appointing Corini, according to a brief club statement which read: "Given the circumstances surrounding the first team, the club feels compelled to appoint a new coach in Eugenio Corini."
Palermo president Zamparini, who bought the club in 2002, is no stranger to upheaval, with Italian media reporting he has overseen close to 60 coaching changes in 29 years as a club owner.
He made a record eight changes last season, when Ballardini was sacked in January before returning in April to oversee Palermo's fight against relegation.
De Zerbi, 37, managed third-division Foggia the past two years and, luckily for him, inserted a clause into his contract that guarantees him a 500,000-euro ($562,000) payout in case of dismissal.
Corini, who counts Torino, Palermo, Juventus and Sampdoria among the clubs he played for, previously coached Crotone, Frosinone and Chievo.