Cumene hydroperoxide (CHP) is prone to thermal decomposition in chemical industry, but there are few reports on the related phenomena in the reactor when decomposition occurs. In order to reveal the complex phenomena of fluid-solid coupled heat transfer, two-phase flow and multi-phase chemical reaction in the CHP decomposition, computational fluid dynamics (CFD) approach was applied to simulate the decomposition of CHP with different mass in a closed pressure vessel. Based on a known reaction scheme and the kinetics evaluated from differential scanning calorimeter (DSC) results, a comprehensive UV model of CHP decomposition was created. As a result, detailed information on the reaction course was obtained, and distribution of temperature, pressure, reaction rate, and flow velocity in the vessel were also investigated. Finally, closed pressure vessel tests (CPVT) were conducted to verify the validity of the CFD model. This work is conducive to deeply understand the thermal decomposition and reactive hazards assessment of CHP.