Musculoskeletal disorders (MSDs) are one of the most serious health problems facing nurses all over the world, but few studies have assessed the prevalence of MSDs together with associated risk factors for nurses representing multiple regions of China. Therefore, the current cross-sectional study investigated 645 registered nurses from four regions of China using a previously validated musculoskeletal survey. Survey includes questions to understand and identify individual characteristics of nurses, biomechanical and psychosocial risk factors associated with MSDs. There was an 84.2% overall 12-month prevalence of MSDs, which were most common in the lower back (73.5%), neck (73.2%) and shoulders (66.2%). A logistic regression including all risk factors was performed for MSDs at each body site. Among individual factors, weekly working hours, gender, BMI, age, and alcohol use significantly affected the odds ratios of MSDs. The most influential biomechanical risk factors identified were cumulative characteristics of the stress, such as time in awkward posture, time of manual material handling, and sustained squat posture. Statistically significant psychosocial risk factors included support from supervisors and/ or colleagues, work control and demands, nurse staffing, and medical device supply. The prevalence of MSDs in Chinese nurses in the current study was high compared with previous studies. Exposures from cumulative physical stresses appeared to increase the risk of MSDs and the development of the associated guidelines on these cumulative exposures is merited. Sufficient nurse staffing, sufficient and proper medical equipment should be provided to reduce the risk of MSDs.