Abstract: Objective : To investigate the change of Ca²⁺ and the mechanism of cooperation between the change of Ca²⁺ and the protease CaspaseD and Caspase8 in BCML - TA 299 breast cancer tissues treated by different methods of giving interferon-a (IFN-a). Methods : At the begining 60 mice were divided into four groups: the intratumoral injection group, subcutaneous injection group, preventive injection group and the control. BCML - TA299 breast cancer tissues was treated by different ways of administration using IFN-a. The DNA content, change of cell cycle and the relationship between the change of Ca²⁺ level and the expression of Caspasse3 and Caspase8 protein were tested. Results : After injection of INF-aby various ways of administration in different groups, the breast cancer cell in each group with BCML - TA299 was observed by method of cell morphology. There was an obvious change of apoptosis in intratumoral injection group. Ca²⁺ showed a very higher level in intratumoral injection group than in the subcutaneous injection and preventive injection group during the apoptotic process.The protease Caspase3 and Caspase8 played an important roles in physical regulation of Ca²⁺ in cell apoptotic process. Conclusions : a) The protease Caspase3 and Caspase8 and Ca²⁺ in cell cooperate in process of regulating the apoptosis in BCML - TA299 breast cancer tissues; b) Different ways of administration can produce various effect on the expression of Caspase3 and Caspase8 and the change of Ca2²⁺ in tumor cells.