Unique environment, coupled with overload, low job control, and high risk might put operating room (OR) nurses in a state of high job strain, which might have negative influences on burnout and organizational commitment. Based on the Job Demand-Control-Support model and previous studies, we hypothesized that the relationship between job strain (determined by job demand and control) and organizational commitment could be mediated by burnout (emotional exhaustion and depersonalization), the effect of job strain on burnout and organizational commitment could be moderated by social support. To verify the hypothesis, a quantitative cross-sectional survey was conducted, 509 OR nurses from 30 tertiary hospitals in Beijing were recruited. Multiple-group path analysis was used to test the moderated role of social support. Propensity score matching was applied to match job strain in different groups. Our research found that in the low social support group, job strain was not related to organizational commitment, while in the high social support group, depersonalization was not related to organizational commitment. Furthermore, nurses in the low social support group were more likely to have depersonalization under job strain compared to the high social support group. Social support should be provided to alleviate the negative impact of job strain.