Role of Traditional Chinese Medicine in Ferroptosis of Liver Cancer: Focus on Signaling Pathways

• Traditional Chinese medicine promotes ferroptosis in liver cancer cells • Thirty-nine recent studies on traditional Chinese medicine–ferroptosis are reviewed • Key targets include NRF2, JAK–STAT, PI3K–AKT–mTOR, p53, MAPK, and AMPK signaling • Traditional Chinese medicine enhances chemosensitivity and reduces drug resistance • Clinical translation challenges and strategies for ferroptosis therapy are outlined . : Primary liver cancer (PLC) is among the most common malignant tumors of the digestive tract, with high incidence and mortality. Hepatocellular carcinoma (HCC) the predominant PLC form has complex pathogenesis. Traditional Chinese medicine(TCM) has gained widespread use as supportive treatment, demonstrating clear efficacy in HCC management. : This article summarizes signaling pathways regulating ferroptosis in HCC cells and systematically reviews current research on pathway modulation by TCM active constituents and compound formulas, emphasizing their cytotoxic effects. HCC cellular survival strategies that evade ferroptosis, including hepatic stellate cell-mediated protective mechanisms, are discussed. Clinical limitations of ferroptosis-based treatments and potential solutions are addressed. : A comprehensive literature search using PubMed, Embase, Web of Science, and Scopus examined signaling pathways in TCM-mediated ferroptosis in HCC cells. Search terms included “hepatocellular carcinoma,” “ferroptosis,” “signaling pathway,” “traditional Chinese medicine,” “TCM monomer,” “TCM formula,” and “TCM extract,” limited to studies from January 2021 to October 2025. Thirty-nine studies were identified: 33 on TCM active ingredients, 1 on TCM extract, and 5 on herbal formulas. : TCM active ingredients and formulas promote ferroptosis in HCC cells through modulation of signaling pathways. Pathway modulation inhibits HCC cell proliferation, invasion, and metastasis; promotes apoptosis; increases chemotherapeutic sensitivity; improves glucose metabolism; and reduces drug resistance. : TCM can induce ferroptosis in HCC cells through multiple pathways, targets, and mechanisms,highlighting its therapeutic advantages and providing guidance for developing novel ferroptosis inducers. .