To promote the practical application of CL-20/HMX co-crystal, the understanding of its thermal decomposition kinetics and thermal hazard prediction are highly required. In this study, the kinetic model was evaluated based on the non-isothermal DSC data by using non-linear optimization method, which was identified as a complicated reaction comprising two parallel autocatalytic paths, and the contribution of the two reaction paths was revealed to vary depending on the heating rate. Based on the kinetic model, the thermal hazard simulation indicates that the temperature when the occurrence of thermal decomposition after 24 h (T-d,T-24) of CL-20/HMX co-crystal is 151.64 degrees C, and the critical temperature of 1000th second explosion is determined as (similar to)1.96 degrees C. Besides, simulation results of self-accelerating decomposition temperature demonstrate that the package mass of CL-20/HMX co-crystal, rather than the package material, has a remarkable effect on the thermal safety of CL-20/HMX co-crystal.