Di-tert-butyl peroxy-hexahydro terephthalate (HTP-65W), a newly developed organic peroxide, has been used in manufacturing acrylonitrile–butadiene–styrene copolymer and as an initiator in the polymerization. However, few studies focus on the thermal hazards of HTP-65W. The purpose of this study was to investigate the thermal decomposition phenomenon of HTP-65W under different conditions via calorimetric technologies and simulation. According to simultaneous thermogravimetric analyzer curves, two mass loss stages were detected at about 79 °C and around 64–72% mass loss happened in the first stage. Furthermore, the real view system was used to observe the apparent physical phenomenon like color and state change in HTP-65W during the reaction. Utilizing accelerating rate calorimeter and adiabatic kinetic method, the exothermic phenomena occurred at around 75 °C. The apparent activation energy (Ea) and rate constant of reaction under adiabatic conditions were 172.0 kJ mol−1 and 4.0 × 1025 mol L−1 s−1. Through differential scanning calorimetry and kinetics simulation, an exothermic peak appeared between 87 and 168 °C caused by the thermal decomposition of HTP-65W, and the Ea calculated using Flynn–Wall–Ozawa and Friedman methods were 143.4 and 128.4 kJ mol−1, respectively. To prevent thermal loss prevention accidents, time to maximum rate under adiabatic condition was obtained as 24 h under 63.9 °C and self-accelerating decomposition temperature was 61 °C for 50 kg package size of HTP-65W. Results of this study can support to prevent the potential thermal hazards of HTP-65W happened during storage, transportation, and manufacturing process.