Anthocyanins belong to a class of flavonoids that exhibit important anti-oxidant and anti-inflammatory actions as well as chemotherapeutic effects. However, little is known concerning the molecular mechanisms by which these activities are exerted. In this study, we investigated the anthocyanins isolated from Vitis coignetiae Pulliat for their potential anti-proliferative and apoptotic effects on human colon cancer HCT-116 cells. These anthocyanins inhibited cell viability and induce apoptotic cell death of HCT-116 cells in a dose-dependent manner. The apoptotic cell death was caspase-dependent and the anthocyanins regulated anti-apoptotic proteins (IAPs). In addition, apoptosis was associated with activation of p38-MAPK and suppression of Akt. In conclusion, this study suggests that the anthocyanins isolated from Vitis coignetiae Pulliat induce apoptosis might at least in part through activating p38-MAPK and suppressing Akt in human colon cancer HCT-116 cells.