Abstract:Ferroptosis is an iron-dependent form of programmed cell death driven by lipid peroxidation and plays a critical role in the initiation, progression, and therapeutic resistance of liver cancer. In recent years, both basic and translational studies focusing on the regulatory network of ferroptosis have advanced substantially. This article systematically reviews the molecular mechanisms of ferroptosis in liver cancer, its subtype heterogeneity, and its interactions with the tumor microenvironment. Particular emphasis is placed on the central roles of the system Xc--GSH-GPX4 axis, dysregulated iron metabolism, and lipid remodeling pathways in ferroptosis regulation in liver cancer. From a therapeutic perspective, ferroptosis inducers, either as monotherapy or in combination with chemotherapy, targeted therapy, immunotherapy, and radiotherapy, have demonstrated synergistic antitumor potential, with some strategies entering early-phase clinical evaluation. In addition, ferroptosis-related biomarkers, such as ACSL4 and FDFT1, are increasingly recognized for their value in prognostic stratification and treatment response prediction. Further studies are warranted to elucidate the dynamic interplay between ferroptosis and the tumor microenvironment, refine biomarker systems, and optimize clinical trial design, thereby accelerating the translational application of ferroptosis-targeted strategies in precision therapy for liver cancer.