This study investigates the mechanism by which pitavastatin induces autophagy-dependent ferroptosis in MDA-MB-231 triple-negative breast cancer (TNBC) cells through the mevalonate pathway. TNBC is a highly aggressive breast cancer subtype with poor prognosis due to its resistance to conventional therapies. Statins, a class of cholesterol-lowering drugs, have shown promising anti-tumor effects, particularly in TNBC and drug-resistant breast cancer cells. The study demonstrates that pitavastatin significantly reduces the viability of TNBC cells, induces cell cycle arrest, and increases oxidative stress. These effects are associated with ferroptosis, a form of regulated cell death characterized by iron-dependent lipid peroxidation. The study reveals that pitavastatin-induced ferroptosis is dependent on the reduction of glutathione peroxidase 4 (GPx4) and ferroptosis suppressor protein 1 (FSP1), and is further enhanced by autophagy. The mevalonate pathway, which is inhibited by statins, plays a critical role in this process. In vivo experiments show that statins can inhibit tumor growth in TNBC-bearing mice, suggesting their potential as a therapeutic option for TNBC patients. The findings highlight the potential of statins as a novel treatment strategy for TNBC by inducing ferroptosis through the mevalonate pathway.This study investigates the mechanism by which pitavastatin induces autophagy-dependent ferroptosis in MDA-MB-231 triple-negative breast cancer (TNBC) cells through the mevalonate pathway. TNBC is a highly aggressive breast cancer subtype with poor prognosis due to its resistance to conventional therapies. Statins, a class of cholesterol-lowering drugs, have shown promising anti-tumor effects, particularly in TNBC and drug-resistant breast cancer cells. The study demonstrates that pitavastatin significantly reduces the viability of TNBC cells, induces cell cycle arrest, and increases oxidative stress. These effects are associated with ferroptosis, a form of regulated cell death characterized by iron-dependent lipid peroxidation. The study reveals that pitavastatin-induced ferroptosis is dependent on the reduction of glutathione peroxidase 4 (GPx4) and ferroptosis suppressor protein 1 (FSP1), and is further enhanced by autophagy. The mevalonate pathway, which is inhibited by statins, plays a critical role in this process. In vivo experiments show that statins can inhibit tumor growth in TNBC-bearing mice, suggesting their potential as a therapeutic option for TNBC patients. The findings highlight the potential of statins as a novel treatment strategy for TNBC by inducing ferroptosis through the mevalonate pathway.