The relationship between targeting protein for xenopus kinesin-like protein 2 (TPX2) expression and triple negative breast cancer (TNBC) has not yet been studied. Herein, patients with confirmed TNBC are evaluated by immunohistochemical staining of TPX2. Our study reveals that elevated TPX2 protein level is significantly associated with worse outcomes, including progression-free and overall survival, in patients with TNBC. In conclusion, we demonstrate that TPX2 could be a novel prognostic marker of progression-free and overall survival in TNBC. Introduction: Triple-negative breast cancer (TNBC), which lacks endocrine therapies and targeted therapies, has the worst prognosis of all breast cancers which remain the most common malignancy in women worldwide. Targeting protein for xenopus kinesin-like protein 2 (TPX2) is a microtubule-associated protein that is strongly correlated with chromosomal instability, resulting in the development of different human tumors. Herein, we investigated the relationship between the clinical outcome of TNBC and the expression level of the TPX2 protein. Materials and Methods: Patients initially treated at Tongji Hospital for confirmed TNBC were evaluated by immunohistochemical staining and retrospectively recruited into our study. The immunohistochemical staining evaluation of TPX2 was based on the staining intensity and extent. STATA was used to analyze all the data. Results: In total, 97 patients with TNBC were recruited into our study. The TPX2 protein was overexpressed in almost all patients with TNBC. Our study demonstrated that an elevated TPX2 protein level was significantly associated with worse outcomes in the patients with TNBC, including worse progression-free survival (PFS) and overall survival (OS) (log-rank test, P<.001). Our model also indicated that TPX2 expression was an independent predictor of OS (hazard ratio, 2.20; 95% confidence interval, 1.13-4.28; P=.020) but not of PFS (P=.639). Conclusion: In conclusion, we demonstrated that TPX2 could be a novel prognostic marker of PFS and OS after the initial treatment of TNBC. We also revealed that TPX2 expression could serve as an independent predictor of OS but not of PFS and a promising therapeutic target in patients with TNBC.