HMX is one of the best high-energy explosives in military applications. In this paper, the reaction calorimeter (RC1e) was used to monitor the reaction process of HMX synthesis by the nitrourea method. The research results show that the heat release rate is large on the reaction feeding stage, the feed rate should be controlled. The thermal parameters, such as adiabatic temperature rise(ΔTad,r) and maximum temperature of the synthesis reaction (MTSR), were calculated for assessing the thermal hazard of HMX synthesis. Although the urea nitrification stage is safer, the operating conditions of other reaction processes also need to be redesigned to improve the process safety level. These studies have potential applications in inherently safer operating measures and safer storage and transportation.