This study aims to investigate the effects of small interference RNA (siRNA) targeting PML-RARα mRNA on the activity of the acute promyelocytic leukemia cell line NB4. The proliferation inhibition was evaluated by MTT assay and colony-formation inhibiting test. Apoptosis was determined by flow cytometry after siRNA treatment. The results showed that the cell growth of siRNA treated group was inhibited, and the apoptosis of NB4 could be induced. The siRNA targeting PML-RARα mRNA might be a valid therapy of acute promyelocytic leukemia.