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The design of automobile human safety is a very important design factor, which the car manufacturers have recently focused. Crash tests have provided information on dummy response measurements such as the maximum chest acceleration head injury criteria (HIC) value and femur loading. The subject of this research is an optimal design of the seat belt in consideration of the deformation behavior of a vehicle cabin with the aim of reducing the human injury. The research focuses on the optimization method of taking the comprehensive trade off between the global approximation and computational cost. The optimization approach called Most Probable Optimal Design (MPOD) proposed by the authors is modified to be applicable to the optimization of cabin crash deformation behavior and safety belt with the mixed discrete and continuous design variables. The application example of the Hybrid III dummy model shows that the MPOD technique is effective in saving the computational cost.