Abstract: he key issue on optimal placement of strain sensors inside the steel beam of cable-stayed bridge was studied for the purpose of the safety evaluation using the structural health monitoring system. A novel optimization method base on the analyses of global and local responses of the multi-scale model of the bridge was proposed, and the Runyang cable-stayed bridge was studied to illustrate the application of the optimization method. The simplified model of the bridge was first developed in order to obtain the key sections of the bridge deck; then, the stress distribution in the global structure and local components were presented by the sub-modeling and multi-scale simulation; finally, the places for installing strain sensors were obtained from the results of the above analyses. The accuracy of the estimated responses indicated by the sensors in the optimal placement was verified indirectly by a comparison between the testing results and simulation results of the static and dynamic response of the bridge.