OBJECTIVE The present study is to evaluate quality of life (QOL) among Chinese medical professionals and explore its main influencing factors. METHODS A total of 2,721 medical professionals were selected from two provinces by using stratified cluster sampling method. The Chinese version of Short Form-36 Health Survey (SF-36) was used to measure QOL; Occupation Stress Inventory-Revised Edition (OSI-R) was used for occupational stress and coping resources. Other potential influencing factors for QOL were collected using a structured questionnaire. Multivariate analysis approach was applied to determine the influencing factors for QOL. RESULTS QOL in the medical professionals was less desirable in comparison with the general population. Occupational stress, long working hour, occupation (being nurse), department (working in surgery) were unfavorable factors for PCS and MCS, and recreation, performance recognized, drinking and physical activity were protective factors for PCS, while rational coping, recreation, social support, performance recognized, drinking and physical activity were favorable factors for MCS. CONCLUSIONS The results suggest that occupational factors, behavioral factors and coping resources, as well as age, play significant roles in QOL in the medical professionals. Accordingly, interventional program designed to target relieving occupational stress, adjusting behavioral habits and increasing coping resources may be useful to improve QOL among medical professionals.