The elasto-dynamics optimal design of 4-UPS-UPU 5-DOF spatial parallel mechanism was studied. The elasto-dynamic models of 4-UPS-UPU spatial parallel mechanism were established based on kineto-elasto dynamics. The total mass function and base frequency function of the parallel mechanism were integrated into a comprehensive optimization objective function, and the restrictive condition of the maximum deformation energy and the maximum dynamic stress of five driving limbs were considered as constraint equations to perform the optimal design. The optimized methods, such as fmincon function in matlab software and genetic algorithms were usedrespectively. The optimal parameters of the mass of moving platform and the sectional area of five driving limbs were determined based on the optimal design. And the correctness and rationality of the optimized method and results were verified.