For finding suitable overall parameters of warhead, the warhead overall parameter optimization was carried out based on lethal area. Establish the related math model, taking the dynamic lethal area as the target function of optimized warhead parameters, and ascertain target function, design variable and constraint conditions, use grid method calculation to satisfy the target function value of constraint conditions, use Matlab to compile optimization calculation program, and acquire influence rule of design variable on lethal area. The calculation results show that the optimized overall parameters combination can effectively improve the lethal area of blast-fragmentation warhead. The method can be used for reference for establishing parameter and designing plan of blast-fragmentation warhead.