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In this paper, a design method is proposed for base isolation system under blast loading that this method is based on transforming design problem into an optimization problem. Genetic algorithm has been employed to solve the optimization problem whereas base isolation system properties have been considered as design variables and a linear combination of base drift and inter-story drift has been defined as objective function. A sensitivity analysis has been also conducted to investigate the effect of base isolation system properties on the blast performance of isolated structure. For numerical simulation, base isolation system is designed using the proposed method for controlling the response of an eight-story nonlinear shear-type building frame under blast loading. It has been found from the results that base isolation system is an effective control system under blast loading that its performance is dependent on the base isolation system characteristics especially the base mass. The optimization results also show that base isolation system designed using the proposed method is a well-designed control system for mitigating the blast response of structure and the proposed design method can be considered as an effective design approach under blast loading.