Ovarian cancer (OC), a common malignancy of the female reproductive system, has the highest mortality rate among gynecological cancers. A distinguishing feature of OC cells (OCCs) is their reduced autophagic flux compared with normal cells. This phenomenon indicates that excessive autophagy activation or impaired autophagosome–lysosome fusion may lead to OCC death. This study investigated the anti-OC effects of dihydrotanshinone I (DHT), a tanshinone compound from Salvia miltiorrhiza. Proteomic analysis suggested that DHT suppressed OC growth via the autophagy–lysosome pathway, with sortilin 1 (SORT1) identified as a critical target. In vitro, DHT promoted autophagosome formation mediated by microtubule-associated protein 1 light chain 3-II (LC3-II), while inhibiting autophagosome–lysosome fusion. The results of an orthotopic OC model corroborated these findings, showing that DHT induced autophagic cell death (ACD) and suppressed SORT1 expression in tumors. Further RNA interference experiments confirmed that SORT1 depletion caused autophagosomes to accumulate in OCCs. Notably, we found that SORT1 interacted with autophagy-related gene (ATG)-encoded proteins ATG5 and ATG16L1, and that depleting SORT1 increased the levels of these proteins. Co-immunoprecipitation, ubiquitination, and cellular thermal shift assay analyses revealed that DHT directly targeted and promoted ubiquitin-dependent degradation of SORT1. By degrading SORT1, ATG5 and ATG16L1 were released, which enhanced autophagosome formation and disrupted the autophagic flux. These findings identified DHT as a novel autophagosome inducer that induced ACD by targeting SORT1, making it a promising therapeutic candidate for OC.