Abstract: Research on the design and optimization of chemical process systems has traditionally focused on thermodynamic efficiency and economic performance, while inherent safety has received comparatively limited attention. However, safety assessment is particularly critical for petrochemical processes operating under severe conditions. Consequently, achieving economic improvement while ensuring process safety has become a key challenge. In this study, the fluid catalytic cracking separation system is selected as the case study. Data samples are generated using process simulation, and the Dow’s fire and explosion index （F&EI） is calculated. The F&EI is incorporated as one of the prediction targets to capture the nonlinear relationship between decision variables and process risk. An optimization framework integrating the non-dominated sorting genetic algorithm II （NSGA-II） is then developed, where the F&EI is imposed as a safety constraint to simultaneously optimize energy consumption and product yield. The Pareto front solution set obtained from the NSGA-II framework is subsequently validated using the process simulation model, and the technique for order preference by similarity to an ideal solution is applied to identify the optimal operating point. The results show that, under the constraint of the risk index, energy consumption is reduced by 21.68% and product yield is increased by 0.59%, achieving a balanced optimization of safety, energy efficiency, and economic performance.