A thermal model of LiNi0.5Mn1.5O4/C electrochemical system has been developed. The thermal model is based on the thermal characteristic and related calculation for full charged LiNi0.5Mn1.5O4 and full discharged carbon materials, respectively. According to simulations on the thermal stability of LiNi0.5Mn1.5O4/C electrochemical system, there is one exothermic process for the full charged LiNi0.5Mn1.5O4 and two for the full discharged carbon. The first exothermic reaction for carbon material should be the best explanation for the initially self-heating of LiNi0.5Mn1.5O4/C electrochemical system. It is the reactions between LiNi0.5Mn1.5O4 and the electrolyte that make the LiNi0.5Mn1.5O4/C cell going into thermal runway. The simulated result shows a good consistency with the testing result, so this simulation method can provide a significant basis for the thermal and safety design of batteries.