The 53-year-old replaces Ivan Juric, who was sacked on Sunday with his side third from bottom of the table having earned six points in their first 12 games of the season.
"Genoa Cricket and Football Club announce the hiring of coach Davide Ballardini to lead the first team," said a club statement. Genoa lost 2-0 at home to Sampdoria on Saturday.
Ballardini was previously in charge during the 2010-11 season and for the second half of the 2012-2013 campaign when he helped save the club from relegation.
Ballardini has also coached Lazio and Bologna and had three stints in charge of Cagliari and Palermo.
(Reporting by Brian Homewood; Editing by Ken Ferris)
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