Objective To investigate the role of phosphoglycerate kinase 1 (PGK1) in tumorigenesis and its potential post-translational modification sites were investigated by bioinformatics method  and molecular biology experimental techniques, in order to provide evidence for PGK1 as a hepatocellular carcinoma(HCC) diagnostic biomarker and therapeutic target.   Methods From pan-cancer’s point of view, 10 967 samples were obtained from the cancer genome database TCGAs, and the expression of PGK1 in different tumors was explored by using cBioPortal and UALCAN analysis tools; Focusing on HCC, the expression differences of PGK1 in hepatocellular carcinoma tumor tissues and normal tissues were further analyzed by using GEO database analysis, Real-time PCR, Western blotting and cell invasion assay；The String database was used to analyze the protein-protein interaction network and gene set enrichment analysis; The CSS-Palm database and bioinformatics method  were used to predict protein post-translational modification sites on PGK1.   Results The PGK1 gene was abnormally amplified and overexpressed in various solid tumors, including hepatocellular carcinoma, and overexpression of PGK1 was correlated with a poor prognosis in hepatocellular carcinoma. Multiple novel post-translational modifications were existed on PGK1.   Conclusion PGK1 is closely related to the occurrence and development of various cancers including HCC and glycolytic metabolism abnormalities. Epigenetic modifications can regulate PGK1 and affect its cellular function in HCC.