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Objective: the latest statistics from the American Cancer Society in 2018 shows that breast cancer is common among cancer diseases and the second leading cause of death among female malignant tumors（14%）[1]. Therefore, a better knowledge of molecular breast carcinogenesis will provide opportunities for designing targeted therapies. Targeting protein for Xenopus kinesin-like protein 2（TPX2） is a microtubule-associated protein required for mitosis and spindle assembly. It has been revealed that TPX2 is overexpressed in various human cancers and promotes cancer progression. Methods: In this study, the differentially expressed genes including TPX2 were screened in GEO database for gene expression microarray of breast cancer. We determined the expression of TPX2 in breast cancer tissues by Immunohistochemistry. Furthermore, we utilize western blot and Quantitative real-time PCR to determine TPX2, Pl3 K, AKT, P21, Caspase-3, Bax and Bcl-2 in breast cancer cells. Cell proliferation, migration and apoptosis rate were respectively measured using CCK8, Transwell assay and flow cytometry. Results: the TPX2 expression level was significantly increased in breast cancer cells and the breast malignant tissues compared with those controls. In vitro experiment further confirmed that knockdown of TPX2 by small hairpin RNA inhibited breast cell proliferation and migration, but induced cell apoptosis. TPX2 silencing decreased the expression of PI3 K and extent of Akt phosphorylation, yet increased expression of P53 and P21. Conclusion: Taken together, our findings indicate that TPX2 silencing negatively regulates the PI3 K/AKT and activates P53 signaling pathway by which breast cancer cells proliferation were inhibited whereas cells apoptosis were accelerated, suggesting that TPX2 may be a potential target for anticancer therapy in breast cancer.