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Objective: To study whether the small-interference RNA (siRNA) targeting against Bcl-2 gene can enhance sensitivity of HL-60 cell to arsenic trioxide. Methods: SiRNA was transferred into the HL-60 cells. At 6 h after transfection, the cells were cultured with arsenic trioxide. The cell growth of the HL-60 cells was detected using MTT at 24, 48 and 72 h, respectively.The levels of the Bcl-2 protein and reactive oxygen species (ROS), as well as of the membrane potential of the mitochondrion were determined by flow cytometry. Results: The Bcl-2 siRNA significantly increased the inhibitory action of arsenic trioxide on growth of HL-60 cells. The combination of siRNA with arsenic trioxide resulted in decrease of the Bcl-2 protein level and increase of the ROS level, as well as significant descending of the membrane potential of mitochondrion of HL-60 (P ＜ 0.05).Conclusion: The siRNAtargeting Bcl-2 can increase the sensitivity of the HL-60 leukemia cells to arsenic trioxide by inhibiting the expression of Bcl-2 protein.