Abstract: OBJECTIVE To analyze and explore the application effect of occupational protection on prevention of hematogenous nosocomial infection. METHODS A total of 186 staff in our hospital from Jun. 2014 to Jun. 2016 were randomly selected as the research subjects, and were divided into two groups according to year, with 93 cases in each group. The medical staff who worked and practiced in our hospital from Jun. 2014 to Apr. 2015 were included into control group, and were given traditional vocational protection education, and the medical staff who worked and practiced in our hospital from Jul. 2015 to Apr. 2016 were included into observation group, and were given optimized vocational protection education. The medical staff perform compliance, qualified rate of occupational protection-related knowledge score, occupational risk protection awareness score, and incidence of hematogenous nosocomial infections were compared between the two groups. RESULTS The perform compliance, qualified rate of occupational protection-related knowledge score, occupational risk protection awareness score and incidence of hematogenous nosocomial infections in observation group were 93.55%, 95.70%, (88.23±4.92) and 2.15%, which were significantly better than 73.12%, 82.80%, (74.18±4.34) and 20.43% in control group (P<0.05). CONCLUSION With the optimization of the content of occupational protection education, it will help to improve the awareness of occupational protection and the awareness of occupational risk prevention, improve the standardized operational compliance and reduce the incidence of hematogenous nosocomial infections, and the clinical application effect is exact.