Glypican-3 (GPC3) is a member of the glypican family, which encodes cell-surface heparan-sulfate proteoglycans, and is frequently upregulated in hepatocellular carcinoma (HCC). We have recently reported that blocking endogenous GPC3 expression promotes the growth of HCC cell lines, suggesting that GPC3 plays a negative role in HCC cell proliferation. Here, we report that forced expression of GPC3 reduced the growth of HCC cells. We also found that FGF2-mediated cell proliferation was inhibited by GPC3. In addition, we observed that the adhesion of HCC cells to collagen type I and fibronectin was decreased by GPC3, whereas cellular migration and invasiveness were stimulated. Collectively, these results suggest that progression of hepatocellular carcinoma is associated with upregulation of GPC3.