Objective To investigate the effects and mechanisms of action of metformin combined with cisplatin on the apoptosis in human colon cancer HCT-8 cells. Methods Human colon cancer HCT-8 cells were divided into four groups: metformin group (MET), cisplatin group (DDP), metformin combined with cisplatin group (MET+DDP),and blank control group (CK). The proliferative ability of HCT-8 cells was determined by an MTT experiment at 24,48 and 72h. The apoptosis rate was determined by flow cytometry at 48 h. Western blotting was used to reveal the expression of apoptosis-related proteins such as bcl-2, Bax and caspase-3 (activated),as well as proteins of the AKT/ GSK-3β pathway at 48 h. Results The cell proliferative ability in the MET+DDP group was weaker than that of the other three groups ( P <0. 05). Moreover, its apoptosis rate was higher than those of the other three groups ( P <0. 05). The expressions of Bax and caspase-3 (activated) was higher than that of the other groups, the expression of Bcl-2, p-AKT and p-GSK-3β was lower than that of the other groups, and the expression of AKT and Gsk-3 was relatively consistent among the four groups.Conclusions Metformin and cisplatin in combination can reduce the activity of the AKT/ GSK-3β signaling pathway, and change the expression of Bcl-2 family proteins,to promote the apoptosis of human colon cancer HCT-8 cells. They also promote the p-caspase-3 conversion to caspase-3 p-caspase-3 conversion to caspase-3 (activated), metformin and cisplatin can thus play a role in promoting the apoptosis of HCT-8 human colon cancer cells.