In order to adapt to the short development cycle of aircraft door seals and the development trend of forward design, this paper simulates, analyzes and optimizes the aircraft door seal based on Abaqus sight software, calibrates the material parameters, puts forward two optimization design methods for aircraft door seal, and obtains a better seal structure through comparison. To better seal structure, the material parameters of rubber and fabric were obtained by experiments, the material parameters were checked based on Abaqus-Isight, and the material parameters were corrected through the compression test curve obtained by the test, so as to get the material parameters with higher fitting degree with the finished product test; Based on Abaqus-Isight pairs of aircraft, the optimization design of cabin door seals was carried out by DOE orthogonal test, with product structural parameters as variables, compression force, contact pressure and friction loss energy as optimization targets, and the local optimal structure could be obtained. The approximate model was obtained by fitting the results of DOE orthogonal test. The global optimal structure can be obtained by using the approximate model algorithm, and better results can be obtained by using the approximate model algorithm for comprehensive evaluation.