Bologna have started the 2022/2023 season with two losses and three draws, and sit 16th on the Serie A table.
Mihajlovic was appointed Bologna manager for a second time in January 2019 but was diagnosed with Leukaemia just six months later. His previous spell in charge of the side lasted from November 2008 to April 2009.
Despite his illness continued to discharge his duties as Bologna manager but suffered a relapse when it returned in March this year following successful treatment the first time round.
Bologna have taken the difficult decision to dispense with the services of the former AC Milan and Fiorentina manager, making him Serie A's first managerial casualty this season.
Bologna president Joey Saputo said in a statement: "It has been the most difficult decision in my tenure here.
"In these years, we have experienced the most beautiful and the hardest moments together that have built not only a strong professional rapport but also a human one.
"Mihajlovic has faced his illness with courage and determination since he explained to everyone his state of health in that very moving press conference.
"Despite his stays in hospital and the heavy effects of the treatment received, he's always remained close to the squad, pushing himself to be in touch with the players, in person or via live conference links.
"Thanks must also be given to the professionalism of his staff, too. The club and the city have joined together to stay close to the head coach in this extremely difficult situation, even if Mihajlovic has always rightly maintained that he wanted to be judged on his professional work.
"Now, unfortunately, the time has arrived to change, which has not been taken lightly but made for the good of the team and the club.
"But even if from today Sinisa Mihajlovic is not the head coach of Bologna, the club and everyone connected to it will forever be by his side in until he has recovered completely and in his future career decisions."
