A thermal-mechanical model for the ignition of a layer of cyclotetramethylene tetranitramine (HMX) particles under drop-weight impact was developed. Considering the micro-particle plasticity, frictional heating, melting, fracture, and chemical reaction at particle level, effects of loading parameters and sample characteristics on ignition and mechanical responses were discussed. The threshold values for ignition to occur under different loading conditions and various material parameters can be predicted. The model was validated by comparing experimental measured and calculated mean pressure-strain curves, which showed two turning points due to localized fragmentation and melting. Relationships between thermal and mechanical responses at the particle level were examined.