Abstract: To investigate changes of mitochondrial membrane potential and the concertration of Ca2+ (Ca2+i) of the HepG2 cells in the process of apoptosis which was induced by agaricus blazei polysaccharide (ABP). HepG2 cells were used as the target cells. Flow cytometry were used to determine the effect of ABP on apoptosis and mitochondrial membrane potential changes. In addition, confocal microscopy was used to test the change of Ca2 + i.The results showed that the apoptosis can be reduced by ABP. ABP played effective role in lowering mitochondrial membrane potential and increasing Ca2+i , which may result in calcium dyshomeostasis finally.The Conclusion that ABP can be used to induce apoptosis of HepG2 cells and the mechanism was related to lowering mitochondrial membrane potential and intracellular Ca2+ overload.