Ferrera arrived at the club in February, after Mario Been was dismissed following a disappointing run of results.
The 47-year-old helped guide Genk to sixth at the end of the 2013-14 regular season, although they finished bottom of the play-off group with just two wins from 10 matches.
On Sunday, Genk went down 3-1 at Mechelen in their season opener, and that has led to the club's board opting for a swift change of approach.
"Genk decided to say goodbye to head coach Emilio Ferrera,"a statement on the club's official website read on Tuesday.
"With everyone looking forward to a fresh start after a difficult season, the first game at Mechelen was surprisingly weak.
"It was decided to discontinue collaboration with Emilo Ferrera immediately.
"Training will be conducted by Pierre Denier until a successor is found."