Objective To observe the effects of small interfering RNA (siRNA)-mediated silencing CacyBP/SIP gene on the apoptosis of human breast cancer cell line MDA-MB-231. Methods Chemically synthesized siRNAs targeting CacyBP/SIP (CacyBP/SIP siRNA) was transfected to MDA-MB-231 cells by LipofectAMINTM2000 (CacyBP/SIP siRNA group). The proliferation of MDA-MB-231 cells was detected by the MTT assay. The apoptosis rate was detected by the flow cytometry. The mRNA and protein expressions of Bcl-2, Bax, and Capase-3 were detected by the Realtime PCR and Western blotting respectively. Besides, the negative control group and blank control group were also established. Results Compared to the negative control group and blank control group, the proliferation rate of MDA-MB-231 cells of the CacyBP/SIP siRNA group significantly decreased (P<0.05), and the apoptosis rate significantly increased (P<0.05). The mRNA and protein expressions of Caspase-3 and Bax significantly increased (P<0.05), while the mRNA and protein expressions of Bcl-2 significantly decreased (P<0.05). Conclusion Targeted silencing CacyBP/SIP gene of breast cancer cell line MDA-MB-231 inhibits the proliferation of MDA-MB-231 cells and induces apoptosis. The mechanism of inducing apoptosis may be relevant to the down-regulation of Bcl-2 expression and up-regulation of Caspase-3 and Bax.