The Casteddu’s loss to fellow strugglers Torino proved to be the final straw for Di Francesco, who leaves the club in the relegation zone and five points from safety.
“Cagliari have parted company with Di Francesco,” read a club statement on Monday afternoon.
“The club have also parted company wit assistant coach Francesco Calzona, assistants Stefano Romano and Giancarlo Marini, fitness coach Nicandro Vizoco and psychologist Gianmaria Palumbo.
“The club thanks all of them for their contribution, commitment, and professionalism.”
Cagliari sit 18th in Serie A with just 15 points from 23 rounds of fixtures so far. Their 1-0 loss to Toro on Friday sees them five points behind the Granata.
Ex-SPAL boss Leonardo Semplici is among the favourites to take the job at the Sardegna Arena.