Objective To observe the application of failure mode and effect analysis (FMEA) in monitoring analysis and protection countermeasures of blood-borne occupational exposure of medical personnel. Methods FMEA was used to retrospectively analyze the high risk factors of blood-borne occupational exposure of medical staff in our hospital from January 2018 to June 2019, to calculate the risk priority number (RPN), to give priority to the highest risk factor, to formulate improvement measures. The improved scheme was adopted from July 2019 to December 2020. The RPN value of failure mode, blood-borne occupational exposure and Chinese Hospital Safety Atmosphere Scale (C-HSCS) before and after the implementating of the scheme were compared and analyzed. Results After implementating FMEA, RPN and weight coefficient (W_i) decreased, and the RPN scores were 2 633 and 853 before and after implementation, with a decrease of 67.60%, W_i was 0.729 9 before implementation and 0.268 0 after implementation, with a decrease of 63.28%. Before FMEA, the blood-borne occupational exposure rate was 28.74%, and after FMEA, the rate was 4.65%. After the implementation, the scores of safety work obstruction was (11.99±2.16), cleanliness and tidiness was (11.48±1.89), management and support was (28.58±3.24), conflict and communication was (22.54±2.83), feedback and training was (13.82±2.55), which were higher than those before the implementation: (10.67±2.68), (10.06±2.36), (26.80±3.86), (20.85±2.62), (12.52±1.19), P<0.05. Conclusions Using FMEA in the management of blood-borne occupational exposure of medical personnel could refine high-risk steps, improve the pertinence of improvement measures and reduce occupational exposure.