In this article, as a potential mechanism for its radio- and chemosensitizing activity, we report that RRx-001 targets CD133+/CD44+ cancer stem cells from three colon cancer cell-lines, HT-29, Caco-2, and HCT116, and inhibits Wnt pathway signalling with downregulation of c-Myc. Here, PROM1 is linked to malignant colon neoplasm.