Objective To investigate the mechanism by which the SLC7A11 gene regulates the development and progression of hepatocellular carcinoma(HCCLM3)through the ferroptosis pathway,and to evaluate its potential as a therapeutic target.Methods Differentially expressed ferroptosis-related genes in liver cancer were screened based on data from the TCGA and ICGC databases.Detection of mRNA expression levels of TERT,MIOX,MYCN,NOX4,and SLC7A11 in tumor and adjacent non-tumorous tissues from 32 clinical liver cancer samples using qRT-PCR.Further analysis of SLC7A11 and its downstream molecules SLC3A2,GSS,and GPX4 was performed through qRT-PCR,Western blot,and IHC to assess expression levels and tissue distribution.A stable SLC7A11-knockdown HCCLM3 cell line was constructed and used to establish a subcutaneous xenograft tumor model in nude mice to evaluate its effect on tumor growth.Mice were divided into two groups(n=6 per group):HCCLM3+sh-NC and HCCLM3+sh-SLC7A11.Serum levels of IL-6,IL-1β,and TNF-α were measured using ELISA.Histopathological changes in tumor tissues were examined by H&E staining,and the expression of key genes was validated through multiple approaches.Results Bioinformatics analysis showed high expression of SLC7A11 in hepatocellular carcinoma tissues(P<0.05),significantly associated with poor patient prognosis.Clinical sample validation revealed significantly higher expression of SLC7A11,SLC3A2,GSS,and GPX4 in cancer tissues compared to control groups(All P<0.05).SLC7A11 knockdown significantly inhibited tumor volume and wet weight(P<0.05),and H&E staining showed reduced vascular density in the sh-SLC7A11 group.ELISA results showed elevated serum levels of IL-1β,IL-6,and TNF-α in the sh-SLC7A11 group.qRT-PCR,Western blot,and IHC all showed significantly downregulated expression of SLC7A11,SLC3A2,GSS,and GPX4 in tumor tissues(All P<0.05).Conclusion SLC7A11 inhibits ferroptosis by regulating the GSH-GPX4 axis,promoting hepatocellular carcinoma cell growth.Targeted inhibition of SLC7A11 can induce tumor cell ferroptosis and suppress tumor progression,suggesting it may be an important therapeutic target for hepatocellular carcinoma.