An electrochemical–thermal coupling model for LiFePO4/C cells is developed by combining White's electrochemical model with thermal model. And the simulations on thermal behavior of LiFePO4/C cells present the entire process from self-heating to thermal runaway, as well as heating sources at each stage based on DSC data. LiFePO4/C cells, using separator with different melting-down temperature have been simulated, and the results show that the inner short circuit, caused by the melting down of separator, is the major factor of thermal runaway of LiFePO4/C cell, in which the separator with lower melting-down temperature has been used. However, when the LiFePO4/C cell employs a separator with higher melting-down temperature, decomposition reactions of electrodes material become the major factor of the safety.