De Canio, who replaced Rolando Maran back in October, was dismissed following Wednesday's 4-1 defeat to Serie B side Siena in the Coppa Italia.
The outcome followed last weekend's 2-1 loss at Atalanta in the league that left Catania at the foot of the standings, four points away from safety at the halfway stage of the campaign.
A statement from the club read: "Catania announces it has released coach Luigi De Canio from his duties as head coach of the first team.
"We wish to thank him for the work done."
Catania are winless on the road this season and have mustered just three victories in 19 games so far.
The Sicilian outfit is set to recall Maran as De Canio's replacement.
De Canio is the third Serie A coach to be sacked this week after Milan dismissed Massimiliano Allegri and Livorno parted company with Davide Nicola.
Catania host Fiorentina on Sunday.
The job was 56-year-old De Canio's 15th managerial appointment, all of which have been in Italy short of a spell in charge of QPR.