Ferroptosis is an iron-dependent, non-apoptotic form of cell death driven by lipid peroxidation, playing a key role in hepatocellular carcinoma (HCC) development. Clinical agents like sorafenib can induce ferroptosis by modulating key pathway factors, suggesting that targeting tumor cell ferroptosis is a promising therapeutic strategy. This review summarizes the prerequisites and defense systems for ferroptosis, drug-mediated ferroptosis mechanisms in HCC, and the differences and connections between ferroptosis and other programmed cell deaths. It aims to provide a theoretical basis, classical inducers, and research progress on ferroptosis in HCC, guiding HCC treatment by regulating the ferroptosis network. Further investigation into ferroptosis mechanisms and interventions at different HCC stages will deepen understanding of HCC and provide new, precise preventive and therapeutic measures. Ferroptosis occurs through lipid metabolism, amino acid metabolism, iron metabolism, and glutathione metabolism. Natural defense mechanisms include enzymatic and non-enzymatic antioxidant systems. Ferroptosis-regulated genes are widely involved in HCC development, and sorafenib resistance is linked to ferroptosis. Ferroptosis is characterized by iron dependence and increased lipid peroxidation, and is involved in cell proliferation, differentiation, and senescence. Ferroptosis can be induced by small molecules or inhibited by lipophilic antioxidants. The main regulatory mechanisms include lipid peroxidation, amino acid metabolism, oxidative stress, iron ion homeostasis, and organelles. The body has a ferroptosis defense system, including Cystine/System Xc-/GSH/GPX4, FSP1-CoQ10-NAD(P)H, DHODH-CoQ10-CoQH2, GCH1/BH4/DHFR, and FSP1/ESCRT-III. Ferroptosis in HCC is regulated by multiple factors, including P53, P62-Keap1-Nrf2-ARE, Rb, MT-1G, S1R, CER, ACSL4, CISD1, HNF4A/HIC1, etc. Classical ferroptosis inducers include erastin, IKE, RSL3, and sorafenib. Erastin inhibits Systems Xc- and induces ferroptosis by reducing GSH levels. IKE improves solubility and anticancer properties. RSL3 inhibits GPX4 and induces ferroptosis. Sorafenib induces ferroptosis by inhibiting SLC7A11 and reducing cystine content. Sulfasalazine induces ferroptosis by inhibiting the Xc-system. Iron-containing statins can promote ferroptosis by inhibiting CoQ10 synthesis and affecting GPX4 activity. Understanding ferroptFerroptosis is an iron-dependent, non-apoptotic form of cell death driven by lipid peroxidation, playing a key role in hepatocellular carcinoma (HCC) development. Clinical agents like sorafenib can induce ferroptosis by modulating key pathway factors, suggesting that targeting tumor cell ferroptosis is a promising therapeutic strategy. This review summarizes the prerequisites and defense systems for ferroptosis, drug-mediated ferroptosis mechanisms in HCC, and the differences and connections between ferroptosis and other programmed cell deaths. It aims to provide a theoretical basis, classical inducers, and research progress on ferroptosis in HCC, guiding HCC treatment by regulating the ferroptosis network. Further investigation into ferroptosis mechanisms and interventions at different HCC stages will deepen understanding of HCC and provide new, precise preventive and therapeutic measures. Ferroptosis occurs through lipid metabolism, amino acid metabolism, iron metabolism, and glutathione metabolism. Natural defense mechanisms include enzymatic and non-enzymatic antioxidant systems. Ferroptosis-regulated genes are widely involved in HCC development, and sorafenib resistance is linked to ferroptosis. Ferroptosis is characterized by iron dependence and increased lipid peroxidation, and is involved in cell proliferation, differentiation, and senescence. Ferroptosis can be induced by small molecules or inhibited by lipophilic antioxidants. The main regulatory mechanisms include lipid peroxidation, amino acid metabolism, oxidative stress, iron ion homeostasis, and organelles. The body has a ferroptosis defense system, including Cystine/System Xc-/GSH/GPX4, FSP1-CoQ10-NAD(P)H, DHODH-CoQ10-CoQH2, GCH1/BH4/DHFR, and FSP1/ESCRT-III. Ferroptosis in HCC is regulated by multiple factors, including P53, P62-Keap1-Nrf2-ARE, Rb, MT-1G, S1R, CER, ACSL4, CISD1, HNF4A/HIC1, etc. Classical ferroptosis inducers include erastin, IKE, RSL3, and sorafenib. Erastin inhibits Systems Xc- and induces ferroptosis by reducing GSH levels. IKE improves solubility and anticancer properties. RSL3 inhibits GPX4 and induces ferroptosis. Sorafenib induces ferroptosis by inhibiting SLC7A11 and reducing cystine content. Sulfasalazine induces ferroptosis by inhibiting the Xc-system. Iron-containing statins can promote ferroptosis by inhibiting CoQ10 synthesis and affecting GPX4 activity. Understanding ferropt