Genoa sit 10th in Serie A but the heavy loss in Naples on Wednesday ended Malesani's tenure. Malesani took charge in June after impressing in a spell with Bologna.
Marino, who has been out of management since he was sacked by Parma in April, has signed a contract until June 30, 2013.
"Genoa has entrusted the conduct of the first team to Pasquale Marino," the club said in a statement on their website.
"The club thanks the coach Alberto Malesani for the work he did during his time at the club."
Marino's tenure at Parma ended with the club perched just two points above the relegation zone, but he remains a respected coach whose CV boasts four promotions and qualification for the UEFA Cup with Udinese in 2008.
"Getting a great club like Genoa is the most beautiful Christmas gift I could imagine," Marino, who also replaced Malesani at Udinese in 2007, said.
"I was contacted this morning. I want to thank the chairman and the club and intend to repay the faith they have shown in me. I'm looking forward to starting work."
Marino will be presented to the media when the team resumes training on December 29.
