On 25 July 2007, Marchisio was loaned out to Empoli for the 2007–08 season with good friend and fellow youth product Sebastian Giovinco to gain first-team experience. He made his Serie A debut on 26 August against Fiorentina and European debut the following month in the UEFA Cup against FC Zürich. Although he did not score any goals, he tallied two vital assists and was a regular starter when available for the Tuscan club under both Luigi Cagni and Alberto Malesani. Unfortunately, Empoli were unable to avoid relegation and he was recalled to Turin by the recently appointed manager Claudio Ranieri.