Club president Enrico Preziosi confirmed the move to the ANSA news agency, adding that talks were under way to hire Luigi Del Neri as a replacement.
Genoa led Roma 2-0 after just 15 minutes Sunday but went on to lose 4-2. The Ligurian club is tied for ninth place, 13 points behind leader Juventus.
De Canio was hired in April to replace Alberto Malesani and he helped Genoa avoid relegation at the end of last season.
Del Neri has coached Chievo Verona, Roma and - most recently - Juventus in 2010-11.
It's the fourth coaching change in Serie A this season.