In present study, we provide novel evidences for first time that human TIPE2 is able to suppress effectively the migration and invasion of HCC in vitro and in vivo and further indicate that human TIPE2 is endogenous inhibitor of Rac1 in HCC by which it reduces F-actin polymerization and expression of MMP9 and uPA. The gene discussed is PLAU; the disease is hepatocellular carcinoma.