Objective: To investigate the interaction between mental elasticityand occupational stress and depressionin female nurses and the mediating effect of mental elasticity, as well as the functioning way of mental elasticity in occupational stress-depression. Methods: From August to October, 2015, cluster sampling was used to select 122 female nurses in a county-level medical institution as study subjects. The Connor-Davidson Resilience Scale (CD-RISC) , Occupational Stress Inventory-Revised Edition (OSI-R) , and Self-Rating Depression Scale (SDS) were used to collect the data on mental elasticity, occupational stress, and depression and analyze their correlation and mediating effect. Results: The 122 female nurses had a mean mental elasticity score of 62.4±15.1, which was significantly lower than the Chinese norm (65.4±13.9) (P<0.05) ; the mean depression score was 41.0±7.7, which was significantly higher than the Chinese norm (33.5±8.6) (P<0.01) , and the incidence rate of depression of 52.5%. Mental elasticity was negatively correlated with occupational stress and depression (r=-0.559 and -0.559, both P<0.01) . Occupational stress and the two subscales mental stress reaction and physical stress reaction were positively correlated with depression (r=0.774, 0.734, and 0.725, all P<0.01) . After adjustment for confounding factors, occupational stress had a positive predictive effect on depression (β=0.744, P<0.01) , and mental elasticity had a negative predictive effect on depression (β=-0.221, P<0.01) . The analysis of mediating effect showed a significant direct effect of occupational stress on depression and a significant mediating effect of mental elasticity (a=-0.527, b=-0.227, c=0.744, c’=0.627; all P<0.01) , and the mediating effect of mental elasticity accounted for 16.08% of the total effect. Conclusion As a partial mediating variable, mental elasticity has an indirect effect on the relationship between occupational stress and depression and can alleviate the adverse effect of occupational stress and reduce the development of depression.