In order to study the ignition process and response characteristics of cast polymer-bonded explosives (PBX) under the action of friction, HMX-based cast PBX explosives were used to carry out friction ignition experiments at a 90° swing angle and obtain the critical ignition loading pressure was 3.7 MPa. Combined with the morphology characterization results of HMX-based cast PBX, the friction temperature rise process was numerically simulated at the macro and micro scale, and the ignition characteristics were judged. The accuracy of the numerical simulation results was ensured based on the experiment. Based on the thermal–mechanical coupling algorithm, the mechanical–thermal response of HMX-based cast PBX tablet under friction was analyzed from the macro scale. The results show that the maximum temperature rise is 55 °C, and the temperature rise of the whole tablet is not enough to ignite the explosive. Based on the random circle and morphology characterization results of tablet, the mesoscopic model of HMX-based cast PBX was constructed, and the microcrack friction formed after interface debonding was introduced into the model. The temperature rise process at the micro scale shows that HMX crystal particles can be ignited at a temperature of 619 K under 4 MPa hydraulic pressure loaded by friction sensitivity instrument. The main reason for friction ignition of HMX-based cast PBX is the friction hot spot generated by microcracks formed after interface damage of the tablet mesoscopic model, and the external friction heat between cast PBX tablet and sliding column has little effect on ignition. External friction affects the ignition of HMX-based cast PBX by influencing the formation of internal cracks and the stress at microcracks.