Objective To investigate the effect of curcumin combined with azacitidine on acute myeloid leukemia cell line KG-1α and explore the possible mechanism.Methods KG-1α cells were treated with curcumin and azacytidine alone or in combination. Cell proliferation inhibition rate was detected by CCK-8 assay, cell cycle and apoptosis were detected by flow cytometry, and the protein expression levels of cell cycle and apoptosis-related proteins and p-AKT were detected by Western blotting. Results The results of CCK-8 assay showed that curcumin and azacitidine alone could inhibit the proliferation of KG-1α cells in a time- and concentration-dependent manner, and the inhibitory rate was significantly increased in the combination group. The results of flow cytometry showed that in the combination group, the cell cycle was significantly arrested in the S phase, and the apoptosis rate was significantly higher than that in the control group and each single drug group. The results of Western blotting showed that compared with the control group, the phosphorylation level of AKT was significantly decreased, the protein expression level of CDK2 was significantly decreased, and the protein expression levels of p27 KIP1, Caspase-3 and γH2A.X were significantly up-regulated in the combination group.Conclusion Curcumin combined with azacitidine significantly inhibited the proliferation of KG-1α cell proliferation, and the mechanism may be related to the down-regulation of AKT phosphorylation level