Liver cancer is the end stage of various chronic liver diseases, with high incidence and mortality rates. Ferroptosis, an iron-dependent form of regulated cell death mediated by excessive lipid peroxidation, plays an important role in HCC pathogenesis, therapeutic response, and drug resistance mechanisms. ADDIN CNKISM.UserStyleExisting studies have shown that traditional Chinese medicine (TCM) and its natural products can induce ferroptosis and influence the occurrence and progression of liver cancer by regulating glutathione peroxidase 4 (GPX4), ferritinophagy, and other related molecular pathways. Notably, some natural products, when combined with sorafenib (SOR), can enhance the sensitivity of liver cancer cells to SOR and reduce SOR resistance by inducing ferroptosis.Therefore, this review summarizes various TCM and active compounds that exert anti-liver cancer effects by inducing ferroptosis or synergistically mitigating chemotherapy resistance, along with their underlying mechanisms. This provides new insights into liver cancer treatment and drug resistance reversal, while also offering potential strategies for developing novel anti-liver cancer drugs.