Triphala churna is a powdered formulation of bioactive compound rich three myrobalan fruits, Emblica officinalis Gaertn. (Amla), Terminalia chebula Retz. (Haritaki), and Terminalia bellirica Roxb. (Bibhitaki) in equal proportions. This formulation has been extensively used in the traditional Indian system of medicine, Ayurveda, for the treatment of several disorders of the gastrointestinal and cardiovascular systems [23–25]. Triphala has also shown to inhibit the growth of carcinogen induced stomach cancer, thymic lymphoma, and pancreatic cancer in mice [26, 27]. However, there are no studies, to our knowledge, regarding the effects of triphala in the colon and specifically against HCCSCs. The aim of the current study was to characterize the antiproliferative and proapoptotic activities of the triphala bioactives on HCCSCs. We hypothesized that triphala bioactives suppress colon cancer stem cell proliferation and elevate apoptosis via suppressing Wnt signaling pathways and induction of mitochondrial mediated apoptosis.