The Stadio Citta del Tricolore outfit sit 18th in the table after taking just 17 points from 21 fixtures so far in their maiden top-flight campaign.
Sunday's 3-1 defeat at 19th-placed Livorno was Sassuolo's sixth loss in their last seven, with their only win since November coming in a dramatic 4-3 triumph over Milan on January 12.
Sassuolo general director Nereo Bonato hinted that Di Francesco's time at the club may be at an end on Monday, and the board has decided to fire the 44-year-old 24 hours later.
Di Francesco, who took on the role in June 2012, will be replaced temporarily by Paolo Mandelli, who has been put in charge of first-team affairs on an interim basis.
A statement on Sassuolo's official website read: "The (club) would like to thank Mr Di Francesco for the important work done in the last 19 months and for the successes that make (him an) indelible part of the history (of) Neroverde."
Sassuolo's next Serie A fixture sees them host Verona on Sunday.
