Social workers are at high risks of experiencing burnout. Despite abundant literature exploring the association between role stress, job autonomy, and burnout, there is a lack of clarity underlying the process that explain how role stress and job autonomy relate to the experience of burnout. Drawing upon a sample of 5,965 social workers in China, this study employed Job-Demands and Resources (JD-R) model as well as stress and coping theory to investigate how role stress and job autonomy are related with burnout through job satisfaction. Structural equation modeling (SEM) was adopted to examine the hypothetical model using AMOS 23.0. The data analysis showed that higher levels of role conflict and role ambiguity were associated with lower job satisfaction, which resulted in higher burnout. Whereas, higher levels of job autonomy were associated higher job satisfaction, which resulted in lower burnout. This study provided implications for human resource management of social work organizations. Reducing role conflict and role ambiguity and improving their job satisfaction combined with increasing job autonomy may be effective in protecting social workers from burnout. Future studies should include social workers in public sector into analysis to enrich our understanding regarding burnout of different groups of social workers.