Abstract: Objective: To study the effect of the siRNA-2 targeting bcl-2 gene on the drug-sensitivity of HL-60 cell to arsenic-trioxide. Methods: SiRNA, a leading sequence selected by previous experiments, was transferred into the HL-60 cells. Six hours later, 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 level of the bcl-2 protein and ROS (reactive oxygen species, ROS), as well as of the membrane potential of the mitochondrion were determined by flow-cytometry. Results: The siRNA significantly increased the inhibitory action of arsenic trioxide on growth of the HL-60 cells. The combination of siRNA with arsenic trioxide resulted in decrease of the bcl-2 protein level and ascensus of the ROS level, as well as significant descending of the membrane potential of mitochondrion of HL-60 (P<0.05). Conclusion: The effective siRNA targeting bcl-2 can increase the drug-sensitivity of the HL-60 leukemic cells to arsenic trioxide by inhibiting the expression of Bcl-2 protein.