Arsenic trioxide (As 2 O 3 ) can induce apoptosis in many tumors. However, the associated mechanisms are not clearly understood. We found that As 2 O 3 significantly inhibited the proliferation of WSU-CLL cells and induced apoptosis in dose- and time-dependent manners. WSU-CLL cells treated with 2μM As 2 O 3 showed survivin down-regulation and p53 up-regulation. Survivin siRNA combined with As 2 O 3 further inhibited the proliferation of WSU-CLL cells. p53 inhibition by siRNA prevented the down-regulation of survivin by As 2 O 3 and prevented the As 2 O 3 -induced cytotoxicity of WSU-CLL cells. These results suggest that As 2 O 3 may be of therapeutic value for chronic lymphocytic leukemia. © 2013 Elsevier Ltd.