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Benzyl isothiocyanate (BITC), which is derived from cruciferous vegetables like garden cress, is a promising cancer chemopreventative phytochemical belonging to the isothiocyanate family with in vivo efficacy in chemically-induced as well as in transgenic rodent models of breast cancer. Cancer chemoprevention by BITC is associated with apoptosis induction in breast cancer cells and suppression of self-renewal of breast cancer stem-like cells (bCSC). This mechanistic study demonstrates a protective role for Krüppel-like factor 4 (KLF4)-p21^CIP1 axis in bCSC inhibition by BITC. The micrograph image shows immunostaining for KLF4 (red color) in BITC-treated MCF-7 cells in which the nuclei are depicted in blue. Translational implication of the findings of this study is that breast cancer chemoprevention by BITC may be augmented with a combination regimen involving BITC and an inhibitor of KLF4.