Rubiae radix is root of Runia akane Nakai, it has been used to hemostasis and blood stasis in Korean and China. This study investigated that anti-oxidant and anti-colorectal cancer effect of ERA (ethanol extract of Rubiae radix) and WRA (water extract of Rubiae radix) using RAW 264.7 (murine macrophage from blood) and HCT-116 cells (human colorectal cancer cell line). ERA contained polyphenol (45.77 ± 2.03 ㎎/g) and flavonoid (22.82 ± 1.33 ㎎/g). 500 μM H2O2-induced ROS generation was diminished by 500 ㎍/㎖ ERA treatment in RAW 264.7 cells, but not WRA (125, 250, and 500 ㎍/㎖). Moreover, caspase-3 activity and DNA fragmentation increased by 500 ㎍/㎖ ERA treatment during apoptotic cell death in HCT-116. Results demonstrated that anti-cancer effect of ERA against human colorectal cancer cells is mediated apoptotic cell death and DNA fragmentation through caspase-3 activation. However, further study is required to what active ingredient of ERA are important for anti-oxidant and anti-colorectal cancer effect in vivo.