Objective To analyze the characteristics of occupational exposure to blood-borne pathogens among health care workers(HCWs), and provide basis for formulating targeted occupational protection strategies. Methods Data of occupational exposure reported by HCWs in a hospital in Southwest China from 2015 to 2019 were retrospectively investigated, the causes, types, sources, disposal and follow-up of occupational exposure were analyzed. Results A total of 411 cases of occupational exposure were reported. Most of the exposed persons were nurses (47.44%), the main exposure departments were internal medicine system (39.41%), surgical system (22.63%) and emergency department (12.41%). The main type of exposure was sharp injury (78.10%, mainly occurred during handling diagnosis and treatment device/medical waste, collecting blood), contacting with skin and mucosa (19.71%), and others (2.19%, mainly caused by scratch and bite). Occupational exposure with unknown source was mainly distributed in emergency department (33.38%), outpatient department (13.89%) and logistics department (8.33%), which was mainly caused during handling of diagnosis and treatment device/medical waste (44.44%), outpatient and emergency injection and transfusion (27.78%), and outpatient blood collection (13.89%). The main sources of blood-borne pathogens were hepatitis B virus, human immunodeficiency virus (HIV) and Treponema pallidum, 70.67% of exposure were treated with drug prophylaxis. Conclusion In the prevention of occupational exposure, more attention should be paid to sharp injury, and training of occupational protection and management of medical waste disposal should be strengthened.