Centromere protein U (CENPU), which is a critical component of the centromere complex, is involved in the cell filament. However, limited research has been conducted on the relationship between CENPU expression and tumors. Immunohistochemical assessment of clinical samples and analysis of TCGA data revealed a positive correlation between CENPU expression and the degree of invasiveness in breast cancer cells. CENPU promoted stem-cell-like behavior and tumorigenicity and induced malignancy in breast cancer cells. Mechanistically, CENPU promoted furin activity by inhibiting its lysosomal degradation. Furin, which is a precursor-processing enzyme of nerve growth factor (NGF), promoted the conversion of proNGF to NGF which could promote breast cancer stem cells in triple-negative breast cancers. . A tumorigenesis assay conducted in a mouse model showed that CENPU promoted tumorigenesis, and treatment with a furin inhibitor suppressed this effect. Our findings revealed that CENPU plays a critical role in furin-mediated signaling responsible for tumorigenesis. Therefore, CENPU may be a novel molecular target in triple-negative breast cancer.