The tendency of psychological depression among social workers is increasingly evident and has become a significant public health concern. We explore the associations between work-family conflict (WFC), role clarity, social support, and psychological depression, with a sample of 944 Chinese female social workers. Our results show that WFC has a significant positive influence on the psychological depression experienced by female social workers, particularly among those who are unmarried. Role clarity serves as a partial mediator between WFC and psychological depression, while social support acts as a positive moderator in mitigating the impact of WFC on psychological depression. Our findings offer both theoretical insights and practical guidance for effectively addressing WFC and psychological depression among female social workers.