In order to study the temperature variation and flow characteristics in the twin-screw reactive extrusion process of synthetizing glycidyl azide polymer-based energetic thermoplastic elastomer (GAP-ETPE), a non-isothermal simulation and a safety analysis were carried out. Firstly, based on the synthesis principle of GAP-ETPE, a mechanical sensitivity test, viscosity test and differential scanning calorimetry (DSC) of GAP-ETPE were carried out. Secondly, a three-dimensional physical model of the intermeshing co-rotating conveying element was established by Gambit. A three-dimensional non-isothermal numerical simulation of the conveying and kneading elements was carried out using FLUENT 19.0 software. The temperature, pressure and shear stress field of conveying and kneading elements with different staggered angles were analyzed and compared. The results show that the maximum temperature of the kneading element is always slightly higher than that of the conveying element at the same rotational speed, but the average temperature in the flow channel is always slightly higher than that of the kneading element. The inlet and outlet pressure difference of the kneading elements with a 90° offset angle is the smallest and the safety is the highest. The shear stress in the flow channel of the conveying element is higher than that of the kneading element as a whole, but the shear stress near the outlet of the 90° kneading element is higher than that in the flow channel of the conveying element. Among the kneading elements, the 90° kneading element has the strongest dispersing and mixing ability, followed by the 60° and 45° kneading elements. According to the thermal and physical parameters of the material, the ignition response time is approximately 6 s, which provides a theoretical guide for the safety design of the GAP-ETPE twin-screw extruder.