Objective To optimize the structure of sealing mechanism by hybrid optimization strategy. Methods The finite element parametric modeling and multi-objective optimization model of sealing mechanism were established. The structure weaknesses of the sealing mechanism were found out through dynamic finite element analysis. And Optimal Latin Hypercube Design ( Opt LHD) was used to study the main parameters affecting the structural strength, the response regularity between the parameters and stress and displacement was analyzed. The base model was built with the help of Opt LHD and was used to optimize the sealing mechanism based on Hybrid Optimization Strategy which contained Multi-Island Genetic Algorithm ( MIGA) and Non-linear Programming by Quadratic Lagrangian ( NLPQL) Algorithm. Results Adjusted R Square was close to 1 in hybrid optimization. The maximum stress and the maximum displacement were decreased to the allowable range. Conclusion Optimal design for sealing mechanism with hybrid optimization strategy is feasible, the result is highly reliable and the effect is apparent.