Objective:To investigate the role of pyruvate kinase M2 (PKM2) on the invasion of liver cancer cell in vitro. Methods:We compared mRNA and protein expressions of PKM2 in hepatocellular carcinoma(HCC) tissues and adjacent normal tissues by real-time PCR and immunohistochemistry. Interfered and overexpressed PKM2 cell lines of HepG2 were constructed to analyze the role of PKM2 on invasion of liver cancer cells. Real-time PCR,immunohistochemistry and Western blot were performed to investigate the expression of HIF-1α and the phosphorylation of STAT3 in HepG2 cells. Results:The mRNA expressions of PKM2 and HIF-1α in the HCC tissues(106/115) were higher than those in adjacent normal tissues. Sample immunohistochemistry showed that the expressions of PKM2 and HIF-1α in HCC tissues were higher than those in adjacent normal tissues. In vitro experiment,interference of PKM2 inhibited the invasion of HepG2 liver cancer cell,and overexpression of PKM2 promoted the invasion of HepG2. The overexpression of PKM2 promoted the phosphorylation of signal transducer and activator of transcription 3(STAT3) and upregulated the expression of HIF-1α. Conclusion:PKM2 upregulates the expression of HIF-1α and promotes liver cancer cell invasion by promoting the phosphorylation of STAT3 and may represent a novel strategy for therapy of HCC.