From 2006 he was head coach of ambitious club Genoa, and led his side to a promotion to Serie A in his first season with the "rossoblu". In the 2008–09 season, Gasperini led Genoa to fifth place of Serie A, the highest placement for the team in 19 years, thus securing a UEFA Europa League spot, relaunching players like Diego Milito and Thiago Motta in a 3–4–3 formation and a particularly spectacular football style that was praised throughout Italy, so much so that José Mourinho, manager of Serie A champions Inter Milan, stated Gasperini was the coach who put him in greatest difficulty. However, a poor start in the 2010–11 season, with 11 points in 10 games despite popular signings such as Luca Toni, Rafinha, Miguel Veloso and Kakha Kaladze, caused Gasperini's dismissal from his coaching post on 8 November.