Objective To explore the role of G protein pathway suppressor 2(GPS2)in regulating proliferation,migration and invasion in hepatocellular carcinoma cell line MHCC-97H.Methods The expression of GPS2 in hepatocellular carcinoma(HCC)cells were detected using quantitative PCR or Western blot;GPS2 was either over-expressed or knocked down in HCC cells using over-expression vectors or short hairpin RNAs(shRNAs)for GPS2,respectively.Clone formation assay,scratch assay and Transwell assay were used to detect the effects of GPS2 on proliferation,migration and invasion of HCC cells.Results In HCC cells,over-expression of GPS2 was found to inhibit the proliferation,migration and invasion of HCC cells MHCC-97H,while knockdown of GPS2 up-regulated proliferation,migration and invasion of MHCC-97H(P＜0.05).The over-expression of GPS2 in MHCC-97H cells was found to inhibit the expression of cell proliferation,migration and invasion-related factors such as EGFR,MMP1,MMP3 and MMP9,while knockdown of GPS2 upregulated the expression of these factors(P＜0.05).Conclusions GPS2 is a novel HCC regulatory factor that inhibits proliferation,migration and invasion of HCC cells.