Purpose -The purpose of this paper is to optimize the key dimensions parameters of the missile suspension structure to ensure the structural fatigue life (> 10000 cycles) with the reliability of 0.995. Design/methodology/approach -The design objective is the fatigue life reliability of the structure, while the design variables are the four fatigue-sensitive dimensions. The nominal stress approach is introduced to predict the fatigue life, and it was verified by comparing with experimental data. The second respond surface method is applied to solve the reliability in a finite element-supported analysis using software MSC Patran/Nastran. A Sequential quadratic programming (SQP) algorithm is used for structure optimization. Findings -The fillet radius r is the most important factor that influences the fatigue life reliability of the structure. The four optimal dimensions parameters are obtained by a reliability-based design optimization process with the fatigue life and reliability fulfilling the demands. Originality/value -The optimal result can be used as the design values for missile suspension structure. The feasibility of the reliability-based design optimization method is validated for the design of missile suspension structure. Keywords Missile suspension structure. Reliability-based design optimization (RBDO), Fatigue life reliability. Sequential quadratic programming (SQP), Structural analysis. Design and theory.