Ferroptosis is a non-apoptotic form of regulated cell death characterized by the accumulation of iron-dependent lipid peroxides in the membrane. It acts as an innate tumor suppressor and is involved in tumor biology. Mesenchymal and dedifferentiated cancer cells are particularly vulnerable to ferroptosis, making it a promising treatment for refractory cancers. Ferroptosis not only inhibits cancer but also promotes cancer development by negatively affecting anticancer immunity. Understanding ferroptosis in cancer is crucial for its clinical application. This review discusses the molecular mechanisms, biological functions, regulatory pathways, and interactions with the tumor microenvironment of ferroptosis. It also summarizes potential applications in immunotherapy, radiotherapy, and systemic therapy, as well as ferroptosis inhibition for cancer treatment. The review highlights the role of ferroptosis markers, current challenges, and future directions in cancer treatment. Ferroptosis is a distinct form of regulated cell death, characterized by iron-dependent lipid peroxidation and the involvement of key enzymes such as GPX4, FSP1, and ALOXs. The mechanisms of ferroptosis involve the synthesis of PUFA-PLs, lipid peroxidation, and iron toxicity. The defense mechanisms include the GPX4 antioxidant system, FSP1/CoQH2, DHODH/CoQH2, and GCH1/BH4 systems. Ferroptosis plays a critical role in tumor suppression and evasion, with tumor suppressors like p53, BAP1, FH, and KEAP1 inducing ferroptosis to suppress tumor growth. Tumor cells evade ferroptosis by upregulating antioxidant systems, such as SLC7A11, GPX4, and NRF2, and by modulating iron metabolism. The RAS signaling pathway is closely linked to ferroptosis, with mutant KRAS upregulating SLC7A11, FASN, and FSP1 to evade ferroptosis. Targeting these pathways offers potential therapeutic strategies for cancer treatment.Ferroptosis is a non-apoptotic form of regulated cell death characterized by the accumulation of iron-dependent lipid peroxides in the membrane. It acts as an innate tumor suppressor and is involved in tumor biology. Mesenchymal and dedifferentiated cancer cells are particularly vulnerable to ferroptosis, making it a promising treatment for refractory cancers. Ferroptosis not only inhibits cancer but also promotes cancer development by negatively affecting anticancer immunity. Understanding ferroptosis in cancer is crucial for its clinical application. This review discusses the molecular mechanisms, biological functions, regulatory pathways, and interactions with the tumor microenvironment of ferroptosis. It also summarizes potential applications in immunotherapy, radiotherapy, and systemic therapy, as well as ferroptosis inhibition for cancer treatment. The review highlights the role of ferroptosis markers, current challenges, and future directions in cancer treatment. Ferroptosis is a distinct form of regulated cell death, characterized by iron-dependent lipid peroxidation and the involvement of key enzymes such as GPX4, FSP1, and ALOXs. The mechanisms of ferroptosis involve the synthesis of PUFA-PLs, lipid peroxidation, and iron toxicity. The defense mechanisms include the GPX4 antioxidant system, FSP1/CoQH2, DHODH/CoQH2, and GCH1/BH4 systems. Ferroptosis plays a critical role in tumor suppression and evasion, with tumor suppressors like p53, BAP1, FH, and KEAP1 inducing ferroptosis to suppress tumor growth. Tumor cells evade ferroptosis by upregulating antioxidant systems, such as SLC7A11, GPX4, and NRF2, and by modulating iron metabolism. The RAS signaling pathway is closely linked to ferroptosis, with mutant KRAS upregulating SLC7A11, FASN, and FSP1 to evade ferroptosis. Targeting these pathways offers potential therapeutic strategies for cancer treatment.