Emerging evidence reveals a dynamic interplay between MDR and ferroptosis: MDR cancer cells suppress ferroptosis through <i>NRF2</i>/<i>GPX4</i>-mediated antioxidant upregulation, iron sequestration by ferritin, and lipid metabolism reprogramming, including <i>SREBP1</i>-driven monounsaturated fatty acid accumulation, while ABC transporters actively efflux ferroptosis inducers. This evidence concerns the gene SREBF1 and cancer.