BIK, a member of the Bcl-2 family, has been reported to induce cell apoptosis but the underlying mechanisms are not well delineated. We used siRNA targeting caspase-12 to examine the effect of caspase-12 on apoptosis induced by BIK. In this study, we show that caspase-12 was activated by BIK. With caspase-12 knocked down, the apoptosis induced by BIK was decreased substantially. The activation of caspase-9 and depolarization of mitochondrial membrane potential were induced by BIK, which were decreased concomitant with caspase-12 silenced.