Abstract: Objective To investigate the effects of demethylation drug decitabine on the apoptosis and cell cycle in acute myelomonocytic leukemia cells in mice and its mechanism. Methods Acute myelomonocytic leukemia cells (WEHI-3) were treated with decitabine (0.25μmol/L) for 3 days. In this study, changes in cell morphology were observed using Wright’s Giemsa staining, apoptosis at different time points of WEHI-3 was measured by Annexin V-PI method, cell cycle change was detected by flow cytometry, mRNA change was detected by Q-PCR. Results After treating WEHI-3 cells with decitabine, the volume of cells increased significantly, with increase of cytoplasm and irregular shape, and the chromatin was concentrated and marginalized. The cell cycle characteristics of PBS treated cells were quantified as follows: G1 phase 39.64%, S phase 49.43%, G2 phase 8.74%. After treatment with decitabine, G1 phase of WEHI-3 cells increased to 78.02%, S phase decreased to 15.86%, and G2 phase decreased to 2.91%, which suggested that WEHI-3 was arrested in G1 phase. The expression levels of MMD, TSG101, TAF7L and CITED2 mRNA in WEHI-3 cells increased significantly after treated by decitabine (all P＜ 0.01). Conclusion Decitabine promotes apoptosis of WEHI-3 cells, and may affect the proliferation of WEHI-3 cells through MMD, CITED2, TAF7L and TSG101. Decitabine can up-regulate the expression of MMD, CITED2, TAF7L and TSG101 genes, induce apoptosis and arrest cell cycle of acute-monocytic leukemia WEHI-3 cells in mice.