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The change of posture, musculoskeletal characteristic and vehicle control parameters resulting from instinctive response were introduced in injury analysis. The key parameters of knee airbag were optimized based on a multi-object optimization algorithm of response surface method and NSGA-II. Results showed that the increased influence of musculoskeletal characteristic happened when the emergency level varied little. Injury in some cases might increase resulting from the early contact between airbag and lower extremity. It decreased in different levels after the optimization of parameters, with maximum 20%. 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