Bcl-3 is an established oncogene in diverse malignant tumors. In this study, we investigated a dual role of Bcl-3 in BL1-subtype triple-negative breast cancer (TNBC). The BL1-subtype TNBC is featured by increasing cell cycle gene expression and the highest sensitivity to chemotherapy among all subtypes. Bcl-3 is associated with a better prognosis in BL1 patients. Bcl-3 knockdown in BL1 cell MDA-MB-468 induces the inhibition of cell proliferation and the G1/S transition arrest by promoting p27 and reducing the expressions of c-Myc and skp2 at mRNA and protein levels. Meanwhile, Bcl-3 enhances the sensitivity of MDA-MB-468 to chemotherapeutics ABX and PTX. Furthermore, the regulation mechanisms are restricted to BL1 cell and do not occur in SUM159PT, a typical MSL subtype of TNBC cell. These data suggest that Bcl-3 may be a potential clinical biomarker for diagnosis, treatment, and prognosis of patients with BL1-subtype TNBC.