Krüppel‐like factor 4 (KLF4) functions as either a tumor suppressor or an oncogene in different tissues by regulating the expression of various genes. The aim of this study was to reveal the functions of KLF4 in regulating breast cancer apoptosis, proliferation, and tumorigenic progression. KLF4 expression levels in breast cancer tissues and breast cancer cell lines were found to be much lower than those in nontumorous tissues and a nontransformed mammary epithelial cell line. KLF4 was upregulated in the tumor necrosis factor‐α–induced SK‐BR‐3 breast cancer cell apoptotic process. Overexpression of KLF4 promoted SK‐BR‐3 breast cancer cell apoptosis and suppressed SK‐BR‐3 cell tumorigenicityin vivo.