During the cook-off of the DNAN-based casting explosives, DNAN will melt, affecting the thermal response of explosives. In order to study the thermal response of DNAN casting mixed explosives under cook-off conditions, casting mixed explosive with the size of Φ30 m×60 m was used for cook-off test out at different heating rates with the method of multi-point temperature measurement. It was found that the temperature of each monitoring point changed with the change of heating rate. In order to study the law of this change, a three-dimensional calculation model of explosives was established and the cook-off behavior under different heating rate was numerically simulated by Fluent. The results show that the heating rate has a great influence on the temperature and ignition position of the explosive phase change and response. With the increase of the heating rate, the temperature of the explosive phase change and the response showed an increasing trend. The temperature at which the explosives undergo phase change was increased logarithmically with the increase of the heating rate. The ignition location of the explosive also moved from the center to the surface of the explosive, affecting the severity of the reaction.