Ferroptosis is a novel type of cell death depending on iron, which has been confirmed strongly related with the development of tumor. Hepatocellular carcinoma (HCC) is a malignancy with high incidence. Despite some reports demonstrated the relation between ferroptosis-related genes and HCC, more details have not been excavated. In present study, we analyzed ferroptosis-related genes with their clinical information from TCGA-LIHC project to find out prognostic genes in HCC. And four genes (GPX2, MT3, PRDX1 and SRXN1) were established as a prognostic model after differentially expressed analysis, Cox regression analyses and LASSO approach. High-risk group separating by cutoff value with poor prognosis was proved, and risk score regarded as an independent prognostic factor. Subsequently, enrichment analyses were processed to the differentially expressed genes, we found that genes generally enriched in ferroptosis-related functions and pathways, also in some immune cells and functions with different immune status. Eventually, we constructed ferroptosis potential index (FPI) to reveal the functional roles of ferroptosis in tumor tissues. The immunohistochemistry performed prognostic genes expression in normal and tumor tissues. In conclusion, these results demonstrated the four-gene signature can be a biomarker for predicting HCC prognosis and its members can be drug target genes for HCC treatment.