On 16 July 2012, De Silvestri was officially loaned to Sampdoria for the 2012–13 season, with Sampdoria having the option to sign him in full following the season. He made his début as a second-half substitute for Gianni Munari against Napoli on 30 September 2012. On 8 May 2013, De Silvestri scored his first goal for Sampdoria by opening the scores in the 1–1 draw against Catania. Following the end of the season, his loan spell was extended for a further season on 12 July 2013. On 18 June 2014, Sampdoria acquired 50% registration rights of De Silvestri. On 25 June 2015 Sampdoria acquired him outright.