Objective To observe the effect of CpG ODN on the chemosensitivity of human acute monocytic leukemia cell line U937 to doxorubicin (ADM) and explore the possible ways to enhance the chemosensitivity of acute leukemia and the mechanism. Method Doxorubicin was used alone and combined with CpG ODN to incubate U937 cells. The growth inhibition rate of U937 cells was detected by CCK-8. Hoechst staining and Annexin VPI double staining were used to detect the apoptosis of U937 cells. The levels of apoptosisrelated genes Bcl2 and Bax were detected by RT-PCR. Results ADM could inhibit the growth of U937 cells, and CpG ODN combined with ADM could further enhance the effect. The growth inhibition rate and early apoptotic rate of U937 cells in ADM+CpG ODN combination group were higher than those in ADM alone group (P＜0.05). The expression of Bax gene in ADM+CpG ODN group was significantly higher than that in ADM group(P＜0.05), but there was no significant difference in the expression of Bcl-2 gene between ADM+CpG ODN group and ADM group (P＞0.05). Therefore, the Bcl-2/Bax value of ADM + CpG ODN combined group was lower than that of ADM single drug group (P＜0.05). Conclusion CpG ODN can enhance the inhibitory effect of ADM on the growth of U937 cells and the apoptotic effect of ADM on leukemia cells, thus enhancing the chemosensitivity of U937 to ADM. This effect may be achieved by upregulating the expression of Bax gene.