The objective of this study was to explore the association between perceived organizational support (POS) and depressive symptoms, and to further explore whether selfefficacy can act as a moderator between POS and depressive symptoms among Chinese petroleum workers. Methods: There was a cross-sectional study conducted at a petrochemical enterprise in Liaoning Province, China, from July to August 2018. A series of questionnaires were accomplished by 1836 petroleum workers, including the Center for Epidemiologic Studies Depression Scale (CES-D), the Survey of Perceived Organizational Support (SPOS), and the General Self-Efficacy Scale (GSES). Hierarchical regression analysis was used to examine the relationship of SPOS score, GSES score, and SPOS score×GSES score interaction with CES-D score. A simple slope analysis will be carried out if the interaction has statistical significance. Results: Hierarchical regression analysis showed that SPOS score (β=−0.538, P<0.01) and GSES score (β=−0.313, P<0.01) played a main influence on CES-D score. The SPOS score×GSES score interaction term significantly explained an extra 9.7% of the variance (F=253.932, adjusted R 2 =0.582, ΔR 2 =0.097, P<0.01). The interaction term was positively correlated with CES-D score (β=0.334, P<0.01). The relationship between SPOS score and CES-D score gradually decreased in the low (1 SD below the mean, β=−0.589, P<0.01), mean (β=−0.338, P<0.01), and high (1 SD above the mean, β=−0.087, P<0.01) groups of GSES score. Conclusion: This study showed that POS and self-efficacy played a main influence on depressive symptoms, and the interaction term was positively correlated with depressive symptoms. Self-efficacy could attenuate the association between POS and depressive symptoms. It suggests that appropriate POS and self-efficacy enhancement measures ought to be supplied to relieve depressive symptoms.