In summary, our study found that TAT-NLS-BLBD-6, a cell-penetrating pentapeptide, blocks the interaction between β-catenin and LEF-1 and also efficiently attenuates tumorigenesis in vitro and in vivo. These results suggest that TAT-NLS-BLBD-6 is an effective Wnt signaling inhibitor and may be a potential therapeutic agent of human breast cancer. Here, LEF1 is linked to breast cancer.