Objective To analyze the expression of ferroptosis-related prognostic genes in hepatocellular carcinoma (HCC) based on single cell sequencing data, so as to provide effective targets for precise treatment of HCC. Methods The Cancer Genome Atlas (TCGA) database and ferroptosis-related gene database were used to obtain ferroptosis-related differentially expressed genes in HCC patients and normal tissue samples, and least absolute shrinkage and selection operator (LASSO) regression analysis was used to construct risk prognosis assessment model. Using single cell sequencing data, we analyzed the expression of prognostic risk genes in HCC cells at different developmental stages by t-distributed stochastic neighbor embedding (tSNE) dimensionality reduction and Monocle package, and the interactions between prognostic risk genes in HCC cells were further analyzed by CellChat package. Results A total of 25 ferroptosis-related differentially expressed genes were found to be associated with the prognosis of HCC patients. And 5'-nucleotidase domain containing 2 (NT5DC2), glucose-6-phosphate dehydrogenase (G6PD), stathmin1 (STMN1) and interleukin 33 (IL-33) were selected as HCC prognostic genes. Among them, NT5DC2 was mainly expressed in epithelial and endothelial cells, IL-33 was mainly expressed in endothelial cells, and G6PD and STMN1 were widely expressed in cells. IL-33 was mainly expressed in endothelial cells at early developmental stages, while NT5DC2, G6PD and STMN were expressed at different developmental stages. Moreover, IL-33 interacted extensively with its receptor only in endothelial cells at early stage of development. Conclusion As a benign prognostic gene, IL-33 is specifically expressed and plays a role in endothelial cells at the early stage of HCC development, suggesting that maintaining this primitive state of vascular endothelial cells or promoting IL-33-mediated primitive endothelial ferroptosis may be an effective therapeutic target for HCC.