An inflatable knee bolster (IKB) is an inflatable airbag cushion deployed in the knee area in conjunction with the frontal airbags to reduce the potential lower-leg injuries. It is conceivable that an IKB can reduce the femur loads. However, its effects on the occupant head and chest injuries and its interaction with the other components of the occupant restraint system are unknown. The goal of this study is to evaluate the potential application of an inflatable knee bolster to improve the occupant safety performance, such as the U.S. new car assessment program (NCAP) star rating. An efficient genetic algorithm method is developed for solving this type of large-scaled, combinatorial, and discrete optimization problems. Genetic algorithm works simultaneously on a population of solution strings according to the survivor of the fitness and provides a population of solutions, which gives more flexibility for engineering implementation and produces a potential global optimal design. The results demonstrate that the genetic algorithm is a useful and applicable tool to optimize design configurations for large-scaled occupant simulation problems.