The weight and number of batteries in the battery engineering vehicle are large, and the overall performance of the vehicle is greatly affected by their layouts. In order to optimize the battery layout of the frame and address the problem of frequently invoking finite element simulation during the optimization process, a battery layout optimization design method combining the response surface approximation model and multi-island genetic algorithm was proposed. Firstly, the parameter optimization model of the battery engineering vehicle frame was established. And the second-order response surface approximation model of the design variables and the objective function was established. Then, the multi-island genetic algorithm was used to solve the optimization model. The dynamic index was used to evaluate the advantages and disadvantages of the solution, and an optimal solution was selected as the optimal battery layout scheme. Finally, the scale frame model was used to verify the optimization results. The results show that the maximum deformation of the frame after battery optimization is reduced by 50.9% , the maximum equivalent force is decreased by 37.9%, the maximum vertical vibration acceleration is reduced by 14. 6% , and the error between the simulation and test results is 7. 1% . The purpose of the optimized design is achieved.