OBJECTIVE To investigate the relationship between the level of caspase-3 and 8 expression and intracellular Ca2+ levels in BCML-TA299 breast cancer cells in the process of apoptosis.METHODS Mice were divided into three IFNa-treated groups and one control group as follows: an intratumoral injection, subcutaneous injection, preventive injection, and a control without injection. The cellular DMA content, changes in the cell cycle and the relationship between the cell Ca2+ concentrations and the expression of caspase-3 and 8 were examined. RESULTS After injection of IFN-α-2b by different routes, the morphologic transformation of the breast cancer cells in each group was observed. There was a typical apoptotic response in the intratumoral-injection group. The expression of caspase-3 and 8 was diverse among the experimental groups, and correlated with the cellular Ca2+ concentration. Caspase-3 and 8 expression and the cellular Ca2+ level were higher following intratumoral injection compared to the other treatments (P＜0.01). Among the experimental groups, the cell cycle displayed definitive changes.CONCLUSION a) Both caspase-3 and 8 and the intracellular Ca2+ are elevated in the process of cell apoptosis in BCML-TA299 breast cancer tissues. These changes may play important roles in the occurrence and development of breast cancer; b) Variation in the route of IFN-α-2b administration can produce different responses in the expression of caspase-3 and 8 and the concentration of Ca2+ in apoptotic tumor cells.