The transition from acute to non-specific chronic low back pain (CLBP) is especially associated with psychological factors. However, working mechanisms of psychological factors have been little examined in non-specific CLBP, especially the mediator effect of pain self-efficacy. Does pain self-efficacy mediate the long-term prediction of work-related factors by depressive symptoms? Within the framework of an exploratory secondary analysis, simple mediation analyses were conducted to longitudinally predict prognosis of gainful employment, as well as subjective physical and mental work ability by depressive symptoms mediated by pain self-efficacy in 382 inpatients with non-specific CLBP. The findings suggest that depressive symptoms prior to rehabilitation predicted levels of all three work-related factors 24months after rehabilitation, and pain self-efficacy 12months after rehabilitation mediated this relationship. To improve the success of work-related rehabilitation in the long-term, pain self-efficacy in particular, but also depressive symptoms should be targeted by treatments of non-specific CLBP.