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Runaway reaction may occur for hexamethylene-diisocyanate (HDI) with two active NCO groups during the reactions or storage and transportation when run into device failure, operation error and other unexpected environments, which would damage equipment or even cause explosions. Adiabatic experiments for HDI using Vent Sizing Package 2 (VSP2) is conducted and temperature and pressure changes over time, as well as the maximum temperature rise rate and maximum pressure rise rate, are obtained. The results show that the initial exothermic temperature of the system is 50°C, and the maximum temperature is 232°C and the heat of reaction is 414.7 kJ/kg, so the severity level of HDI is classified as "medium" according to the assessment criteria for the severity of a runaway reaction. The relief type of the reaction system is determined to be a gas system by analysis of the pressure change curve during heating and cooling processes, along with the temperature at the point of loss of control, and calculated by the DIERS method and Leung's correction method through Python programming, which is applied to determine the required safety relief device for an industrial scenarios, and the minimum relief area is calculated to be 0.0028m2 and 0.0019m2, respectively. The study verifies the higher reliability of the safety relief design for runaway reactions based on VSP2 experimental data.