Abstract: Apoptosis is a form of programmed cell death controlled genetically in response to apoptotic stimuli or signals. Apoptosis induced by mitochondrial pathway is mainly regulated by the complex interplay between B-cell lymphoma 2 (Bcl-2) protein family members. However, the detailed interplay mode remains debatable. In this paper, the molecular mechanism of the interaction between Bcl-2 family members was firstly reviewed. Secondly, the mathematical models were summarized about bistability emerged from apoptosis and the interaction mode of Bcl-2 family proteins, respectively. Finally, numerical simulations and bifurcation analysis were conducted for the three interplay modes(i.e. direct activation mode, indirect activation mode and unified mode) proposed by the biologists. The results are in favor of the unified mode as a most plausible interplay mode. The work is hoped to improve our understanding of the molecular mechanism in the pathological cells and to provide insights into the manipulation of the diseases caused by abnormal apoptosis, such as cancer and Alzheimer's disease.