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Rigid-flexible printed circuit boards (RFPCB) has the advantages of providing not only the flexibility and bendability required by many electronic products, but also the reliability required by the key electronic components. In this study, based on one kind of RFPCB which would be used for a wearable device prototype, the structure optimization was performed by simulations. Through the structural analysis, it is found that there are some risk places for potential failures, such as the corners of the connecting part of the RFPCB. Normally, the stress concentrations would locate on these places if the circuit boards encounter the bending, twisting or tension conditions during the assembly process or usages. Hence the three load conditions are simultaneously considered in the optimization. To reduce the stress concentration in the corners of connecting part, the structure of the FPC cross section were optimized. The various optimization proposals are presented firstly. Then the simulations were executed. At last, by comparing the maximum Von Mises stress of different simulation cases, the optimized structure was attained. Appending substrate layers on top and bottom layer of FPC and setting air gap between the appending substrate and FPC is suggested using tension and twisting cases. The original design is better used under the loading condition of bending.