This paper investigates the reliability design optimization of an aeronautical hydraulic pipeline system, in which the constraint locations are treated as design parameters. To reduce the size of the optimization problem, two non-probabilistic global sensitivity indices are introduced and modified to screen out those constraint locations which have no or little effect on the optimization target. Considering the rest of constraint locations as design variables, the complexity of the optimization problem is dramatically reduced. The optimization of the pipeline systems demonstrates that the proposed method is superior to the traditional direct optimization method in both the optimization efficiency and results. This work indicates that introduction of sensitivity analysis can greatly improve the efficiency and performance of optimization, especially in those complex engineering problems involving a large number of design variables.