Nicola was sacked on January 18 following an 8-2 defeat to Atalanta but in a bizarre twist of events was re-hired just two days later.
Since Nicola's re-appointment, Salernitana have lost three times in four Serie A games and now sit in 16th place, five points above the relegation zone.
A 1-0 defeat to fellow strugglers Hellas Verona on Monday has seen Nicola get the sack once again.
Former Fiorentina boss Paulo Sousa has been charged with keeping Salernitana in the top flight, with his appointment confirmed swiftly after Nicola's dismissal on Thursday.
The Serie A minnows stated: "US Salernitana 1919 announces that it has reached an agreement with Mr. Paulo Sousa and has entrusted him with the technical guidance of the first team".
Meanwhile, they also said of Nicola: "US Salernitana 1919 announces that it has relieved Mr. Davide Nicola of his post as coach of the First Team.
"In thanking him for his passion and dedication to work, the Club wishes the technician the best professional fortunes for the continuation of his career".
Salernitana's next game is against Lazio this weekend.
