Depression is one of the most common mental health problems among people living with HIV (PLWH). However, the longitudinal psychological mechanism underlying the link of internalized HIV stigma and depressive symptoms remains a research gap. This study attempted to articulate how and to what extent perceived social support and resilience mediate the longitudinal associations between internalized HIV stigma and depressive symptoms. A sample consisting of 1,098 Chinese PLWH (Mage = 38.63, SD = 9.20; 63.9% male) with a six-month interval and four waves of follow-up was used in the current study. Participants were asked to complete self-report questionnaires. The associations among main study variables were examined via a complete longitudinal mediation approach. Results indicated that the linkage between internalized HIV stigma at T1 and depressive symptoms at T4 was serially mediated by perceived social support at T2 and resilience at T3, and perceived social support at T2 and depressive symptoms at T3 serially mediated the relationship between resilience at T1 and internalized HIV stigma at T4. Depressive symptoms at a previous time point consistently predicted the levels of internalized HIV stigma at subsequent time points. The study highlights the complex interplay between internalized HIV stigma, mental health problems, and protective factors in a longitudinal context. The findings suggest the need to incorporate interventions aimed at enhancing social support and resilience in mental health programs for PLWH, as these factors may interrupt the pathway from internalized HIV stigma to depressive symptoms and potentially improve the overall psychological well-being of this population.