Hepatocellular carcinoma (HCC), a common type of liver cancer, is increasing in incidence worldwide. An early diagnosis of hepatocellular carcinoma (HCC) is still challenging: Currently, few biomarkers are available to diagnose the early stage of HCC, therefore, additional prognostic biomarkers are required to identify potential risk factors. The present study analyzed gene expression levels of HCC tissue samples and the protein expression levels obtained from the GSE46408 HCC dataset using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses. The metabolically associated differentially expressed genes (DEGs), including DEGs involved in the glucose metabolism pathway, were selected for further analysis. Phosphoglycerate kinase 1 (PGK1), a glycolytic enzyme, was determined as a potential prognostic biomarker through Kaplan-Meier curve and clinical association variable analyses. This was also verified based on the expression levels of PGK1 in tumor tissue and protein expression levels in several liver cancer cell lines. PGK1 mRNA demonstrated a high level of expression in HCC tissue and was significantly associated with a poor prognosis, showing a negative association with survival time. In addition, as an independent risk factor, PGK1 may potentially be a valuable prognostic biomarker for patients with HCC. Furthermore, expression of PGK1 was associated with the early stages (stage I and T1) of HCC. Moreover, PGK1 mRNA expression levels demonstrated a positive association with progression of liver cancer. The results suggested that PGK1 mRNA may be involved in the degree of HCC malignancy and may be a future potential prognostic biomarker for HCC progression.Copyright: © Yi et al.