To improve the design level and R＆D efficiency of large-span inflatable structure, an optimization method combining FEM with genetic algorithms is applied to design optimization of large span inflatable structure. A FEM model of the inflatable structure is established, calculated and analyzed with the FEM software ABAQUS, then the model is optimized with genetic algorithms and the optimal solution is obtained after breeding and evolution. From the analysis results, there are uniform stress distribution on skin material, higher average stress levels on each accessory structure, a high material utilization and the weight 3 928 kg of whole structure in the optimal solution. According to the optimal solution, the sample is processed and tested, and it can safely work under all conditions. The minimum safety distance of rotor wingtip is 1.09 m, and the minimum vertical safety distance is 1.67 m, which are consistent with the results of FEM. The test results are almost consistent with the analysis, and the optimization program meets the practical requirements well.