Programmed cell death (PCD) is thought to have multiple roles in tumors. Here, the roles of PCD-related genes were comprehensively analyzed to evaluate their values in hepatocellular carcinoma (HCC) diagnosis and prognosis. Gene expression and single-cell data of HCC patients, and PCD-related genes were collected from public databases. The diagnostic and prognostic roles of differentially expressed PCD-related genes in HCC were explored by univariate and multivariate Cox regression analyses. Single-cell data were further analyzed for the immune cells and expression of feature genes. Finally, we evaluated the expression of genes by quantitative real-time polymerase chain reaction and Western blot, and the proportion of immune cells was detected by flow cytometry in HCC samples. We obtained 52 differentially expressed PCD-related genes in HCC, based on which the consensus clustering analysis cluster 2 was found to have a worse prognosis than cluster 1. Then 10 feature genes were identified using LASSO analysis, and programmed cell death index (PCDI) was calculated to divided HCC patients into high-PCDI and low-PCDI groups. Worse prognosis was observed in high-PCDI group. Cox regression analysis showed that PCDI is an independent prognostic risk factor for HCC patients. Additionally, SERPINE1 and G6PD of feature genes significantly affect patient survival. Macrophages and Tregs were significantly positively correlated with PCDI. G6PD mainly expressed in macrophages, SERPINE1 mainly expressed in fibroblast. The experimental results confirmed the high expression of SERPINE1 and G6PD in HCC compared with the control, and the infiltration level of macrophages and Treg in HCC was also obviously elevated. PCDI may be a new predictor for the diagnosis of patients with HCC. The association of SERPINE1 and G6PD with the immune environment will provide new clues for HCC therapy.