Breast cancer, especially triple-negative breast cancer (TNBC), has limited treatment options. We repurposed the FDA-approved drug bazedoxifene as a novel inhibitor of interleukin 6/glycoprotein 130 signaling. In this study, we investigated the inhibitory effects of bazedoxifene alone or in combination with paclitaxel on several estrogen receptor positive and TNBC cells. Bazedoxifene inhibited the cell viability of these cells, as well as tumor growth of TNBC cells in a xenograft tumor model. Furthermore, bazedoxifene combined with paclitaxel exhibited more potent inhibition of cell viability, colony formation, and cell migration and induced more apoptosis in vitro, and generated stronger inhibition of tumor growth of TNBC in vivo than either drug alone. Western blotting showed that bazedoxifene inhibited estrogen receptor positive breast cancer cells by suppressing the expression of estrogen receptor, Cyclin D1, p-P70S6K, Survivin, c-Myc, and Bcl-2, and bazedoxifene inhibited TNBC cells by inhibiting the expression of phosphorylated STAT3((Tyr705)), Cyclin D1, p-P70S6K, c-Myc, p-AKT((Ser473)) and p-ERK 1/2((T202/Y 204)) without changing the expression of total STAT3. When combined with paclitaxel, bazedoxifene may be a potential small molecule for the treatment of both estrogen receptor positive and triple-negative breast cancer.