Epimedium koreanum Nakai has been used in traditional medicine as an aphrodisiac, hypotensive, and neurasthenia;however, the cellular mechanism of E. koreanum Nakai cultivated in North Korea on HCT116 colon cancer cellactivity has not been investigated. This study is to investigate the effect of E. koreanum Nakai on apoptosis of thehuman colon cancer cell line HCT116. The anti-proliferative activity of E. koreanum Nakai on HCT116 was iden-tified through MTT, Western Blot, and RT-PCR analyses. The results show that 70% ethyl alcohol extracts of E.koreanum Nakai inhibited the growth of HCT116 colon cancer cells (IC50: 1.2mg/mL on 24 hr). Concomitant acti-vation of the mitochondria-dependent apoptotic pathway occurred via modulation of Bcl-2 and Bax expressions,resulting in activation of cleaved caspase-3 and cleaved caspase-9.