Abstract: Objective: To explore the potential mechanisms of BH₃ mimic analogue BH₃I-2'-in-duced apoptosis in leukemic cells and to offer evidence for clinical application of the anti-cancerdrugs.Methods: The flow cytometry, ELISA and Western blotting methods were applied to detect theapoptosis and change of mitochondrial membrane potential and ROS generation, activity of NF-κB, ex-pression of Bcl-XL and Survivin proteins in K562 and CEM cells after treatment with BH₃I-2'.Re-sults: The apoptosis in leukemic cells was significantly induced by BH₃I-2', thus resulting in decreaseof mitochondrial △Ψm、generation of ROS and up-regulation of NF-κB and anti-apoptosis proteins(Bcl-XL, Survivin).Conclusions: Through the damages of mitochondrial inner membrane by causingthe collapse of mitochondrial △Ψm and the generation of ROS, the BH₃I-2'could induce apoptosis bythe mitochondrial pathway. Furthermore it can activate the NF-κB and anti-apoptosis proteins simulta-neously. So we should also pay more attention on the cell-self-protective mechanisms when the drugsinduce the apoptosis.