To optimize titanium alloy beam seal with elliptical arc groove, based on ABAQUS software, the elastic-plastic contact finite element model of the beam seal was established, and the contact stress distribution and contact bandwidth of the two seals between the male and female connectors were obtained. Taking S index as the evaluation criterion of sealing performance, which considers both the macro geometry of the beam seal and micro morphology of the contact surface, the female connector with the best sealing performance is obtained by using ISIGHT software and multi-island genetic algorithm. The simulation demonstrates that its S index is 102.2% higher than that of the prototype, 53.1% higher than the maximum in the database, and its maximum contact pressure and contact bandwidth are remarkably increased, which means that the sealing performance of the optimized geometry is significantly improved. The S index of optimized beam seal is in good agreement with the prediction value of the optimization method, which verifies the effectiveness of the optimization method and the accuracy of the optimized geometry. Compared with the traditional method of evaluating the sealing performance only by contact stress or contact width, the S index comprehensively considers the macro and micro characteristics of the seal and provides a quantifiable sealing performance objective function for the optimization design of the beam seal. The application of ISIGHT software and multi-island genetic algorithm can improve the calculation efficiency and optimization accuracy.