Sassuolo have lost all five league games since Malesani replaced Di Francesco in late January and, with 12 games to go, the club have put their faith back in the coach who guided them to the top flight.
Malesani's tenure lasted only 33 days and Di Francesco has been handed the task of stopping Sassuolo's slide towards Serie B.
A statement on the club's official website read: "Sassuolo announces that it has removed Alberto Malesani as coach of the first team.
"Malesani deserves thanks for the professionalism and commitment during this difficult stage of the championship.
"Coaching of the first team will be entrusted to Eusebio Di Francesco."
Di Francesco mastermind the club's first promotion to the top flight last term after winning Serie B by three points.
The Italian also guided Sassuolo - currently four points adrift of safety - to victories over Milan, Sampdoria, Atalanta and Bologna this season.
