Objective:To explore the role of Bcl2 and Caspase3 in modulating apoptosis of ERnegative breast cancer cells induced by tamoxifen. Methods:ERnegative breast cancer cell lines MDAMB231 were treated with 10.0μM tamoxifen for 12, 24, 36、48, 60 hours. The rate of cell apoptosis with or without caspase3 inhibitor AcDEVDCHO, and protein expression of Bcl2，Bax were determined by flow cytometry, and the activity of Caspase3 was examined with fluorophotometry. Results:The expression of Bcl2 was downregulated, the activity of Caspase3 and the rate of cell apoptosis were increased by TAM timedependently, and the rate of apoptosis reached its peak at 48 hours. The expression of Bcl2 was negatively correlated with activity of caspase3. Tamoxifen, however, did not affect Bax protein expression. AcDEVDCHO, a caspase3 inhibitor, blocked the activation of caspase3 and inhibited cell apoptosis induced by tamoxifen. Conclusions:TAM could induce apoptosis in ERnegative breast cancer cells via mitochondria pathway by downregulating Bcl2 expression, and the activation of Caspase3 might play an important role in the process of tamoxifeninduced apoptosis of ERnegative breast cancer cells.