Abstract: OBJECTIVE To explore the comprehensive strategies for effective prevention and control of spread of infection in medical institutions, especially for the front-line medical staff's occupational exposure to COVID-19 during the clinical treatment. METHODS The risk of occupational exposure of the medical staff and the effectiveness of the prevention and control measures were systematically evaluated based on the legal rules and guidelines for occupational exposure to infectious diseases and the problems that were found during onsite supervision such as 'three zones and two channels' management and strict zoning prevention and control for individual protection. RESULTS The legal and scientific requirements for prevention and control were implemented, and it is necessary to adhere to systemic thinking and bottom line thinking, intensify the idea of 'prevention first, scientific response', take comprehensive measures by prioritizing the risk of occupational exposure, carry out reasonable personal protection measures and avoid insufficient and excessive protection. CONCLUSION In addition to the reasonable use of personal protective articles, it is necessary to scientifically and standardly implement more effective prevention and control measures for occupational exposure to infectious diseases and intensify the engineering control, management control and behavior control during the prevention and control of infection.