Hepatocellular carcinoma (HCC) is a highly prevalent malignant tumor that is associated with substantial morbidity and mortality rates. Despite the progress made in diagnostic technology, the survival rate of HCC patients remains unsatisfactory due to the complex nature and extensive metastasis of the disease. Consequently, the discovery of new molecular targets is of great practical significance for the diagnosis and treatment of HCC. Protein tyrosine phosphatases (PTPs) play a crucial role in cell signal transduction by catalyzing the dephosphorylation of tyrosine residues in proteins. The present study has revealed that the upregulation of protein tyrosine phosphatase non-receptor type 1 (PTPN1) is a characteristic feature of HCC and is associated with a poor prognosis. Additionally, our investigation into the functional roles of PTPN1-regulated genes in HCC has demonstrated that alterations in PTPN1 expression disrupt normal cell cycle progression metabolism. Additionally, the capacity for proliferation and migration of HCC cells was notably diminished subsequent to PTPN1 silencing, resulting in the prevention of cell entry into the S phase from the G1 phase. Our investigation indicates that PTPN1 may facilitate the onset and progression of HCC by disrupting the cell cycle, thereby presenting a promising molecular target for the diagnosis and treatment of liver cancer.