This paper mainly discusses how to do a good job of daily biosafety protection measures in clinical microbiology laboratories during the epidemic of COVID-19, so as to ensure the safe development of routine clinical microbiology testing items. According to the microbiological and epidemiological characteristics of the novel coronavirus, this paper analyzed the potential risks of the laboratory from the perspective of personal protection before, during, and after testing. Combined with the actual work situation, the improved biosafety protection measures and optimized work flow are introduced to ensure the safety of medical staff and the smooth development of daily work. Danyang People’s Hospital of Jiangsu Province, clinical microbiology laboratory of clinical laboratory in strict accordance with the relevant laws and regulations, technical specifications and the expert consensus, combined with their own conditions, the biosafety measures to perfect the working process was optimized, effectively prevent the laboratory exposure, and maintain strict working condition for a long time, continue to improve. We found that the biosafety protection measures of clinical microbiology laboratory have good prevention and control effect on preventing infection of medical staff, which will greatly reduce the risk of infection of medical staff, form good working habits, and provide reference for biosafety protection of microbiology laboratory during the epidemic of COVID-19.