The most widespread type of liver cancer, HCC, is associated with disabled cellular death pathways. Despite therapeutic advancements, resistance to current systemic treatments (including sorafenib) compromises the prognosis of patients with HCC, driving the search for agents that might target novel cell death pathways. Ferroptosis, a form of iron-mediated nonapoptotic cell death, has gained considerable attention as a potential target for cancer therapy, especially in HCC. The role of ferroptosis in HCC is complex and diverse. On one hand, ferroptosis can contribute to the progression of HCC through its involvement in both acute and chronic liver conditions. In contrast, having ferroptosis affect HCC cells might be desirable. This review examines the role of ferroptosis in HCC from cellular, animal, and human perspectives while examining its mechanisms, regulation, biomarkers, and clinical implications.
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