Objective: Targeting protein for Xenopus kinesin-like protein 2(TPX2) is a nuclear proliferation-related protein that plays a critical role in the formation of mitotic spindle. High expression of TPX2 has been observed in several types of tumors. However, the role of TPX2 in hepatocellular carcinoma(HCC) remains unclear. Our study aimed to investigate the effect of TPX2 on HCC cell invasion.Methods: The immortalized normal human liver cell line L02 and six HCC cell lines including SMMC-7721, BEL-7402, Huh-7, HepG2, Hep3 B and SKHep1 were subjected to qRT-PCR and western blot for TPX2 mRNA and protein, respectively. Furthermore, TPX2 small interfering RNA(siRNA) was used to knock down TPX2 expression in SMMC-7721 and HepG2 cells. Cell proliferation and invasion were determined by MTT and transwell assays. Otherwise, expression of p-AKT, MMP2 and MMP9 were evaluated by western blot in SMMC-7721 cells.Results: The expression of TPX2 in HCC cell lines was markedly higher than that in normal human liver cell line. TPX2 knockdown using a specific TPX2-siRNA reduced the number of invaded cells and inhibited cell proliferation in SMMC-7721 and HepG2 cells. Furthermore, TPX2 knockdown resulted in inactivation of AKT signaling and down-regulation of MMP2 and MMP9 expression in SMMC-7721 cells.Conclusions: Our study identified that TPX2 might contribute to tumor cell invasion through activating AKT signaling and subsequently increasing MMP2 and MMP9 in HCC. Objective: Targeting protein for Xenopus kinesin-like protein 2 (TPX2) is a nuclear proliferation-related protein that plays a critical role in the formation of mitotic spindle. High expression of TPX2 has been observed in several types of tumors. However, the role of TPX2 in HCC cell invasion. Methods: The immortalized normal human liver cell line L02 and six HCC cell lines including SMMC-7721, BEL-7402, Huh -7, HepG2, Hep3 B and SKHep1 were subjected to qRT-PCR and western blot for TPX2 mRNA and respectively, respectively. TPX2 small interfering RNA (siRNA) was used to knock down TPX2 expression in SMMC-7721 and HepG2 cells. Cell proliferation and invasion were determined by MTT and transwell assays. Otherwise, expression of p-AKT, MMP2 and MMP9 were evaluated by western blot in SMMC-7721 cells. Results: The expression of TPX2 in HCC cell lines was markedly higher than that in norma TPX2 knockdown resulted in inactivation of AKT signaling and down-regulation of MMP2 and MMP9 expression in SMMC-7721 cells. Conclusions: Our study identified that TPX2 might contribute to tumor cell invasion through activating AKT signaling and subsequently increasing MMP2 and MMP9 in HCC.