It was recently reported that arsenic trioxide (As(2)O(3)) can induce complete remission in patients with acute promyelocytic leukemia (APL). In this present article, the biological effect of (As(2)O(3)) on human cervical cancer HeLa cells and HeLa cells overexpressing Bcl-2 is studied. By MTT and colony forming ability assays, morphology alteration, flow cytometric analysis, DNA gel electrophoresis and in situ cell death detection (TUNEL), it was found that As(2)O(3) inhibited the growth of HeLa cells and induced G2/M arrest and apoptosis of the cells. RT-PCR, Northern blot, Western blot analysis revealed that As(2)O(3) induced HeLa cell apoptosis possibly via decreasing the expression of c-myc and viral genes. HeLa cells overexpressing Bcl-2 partly resist As(2)O(3) induced apoptosis, which might be relative to preventing the cells from As(2)O(3) caused G2/M block, downregulation of c-myc gene expression and inhibition of viral gene expression was also noted. However, it was found that As(2)O(3) at a high concentration could also induce apoptosis of HeLa cells overexpressing Bcl-2 possibly mainly via downregulating Bcl-2 expression and slightly inhibiting viral gene expression.