Equivalent design wave (EDW) and spectral analysis are two methods to predict the stress in the Semi-submersible hull of floating offshore wind turbine (FOWT). Compared with spectral analysis, EDW save the cost of finite element calculation, while its accuracy depends on the selection of global response and the method used to select EDWs. To investigate the effect of equivalent design wave selection on the stress prediction, EDW analysis with different selection of governing loads and spectral analysis are conducted for FOWT Semi-submersible (Semi-sub) hull. In this study, a typical 5 MW Semi-sub FOWT is selected and the finite element (FE) model of hull is constructed. Hydro-structure interaction analysis of the hull is conducted, with the hydrodynamic pressure recalculated at structural points, and different pressure components separately transferred from the hydrodynamic to structural model. The frequency, amplitude, wave heading of EDWs are selected according to the long-term spectral analysis results of the global response. The results indicate that in practical EDW analysis, in addition to selecting internal load and inertial load as governing loads according to the specifications, the pressure, velocity, and hydrodynamic coefficients should also be considered to enhance the accuracy of EDW predictions. Most of the EDWs are concentrated around a specific frequency and heading, which is related to structural type and geometric dimension. These findings will provide a reference for the selection of design waves and the design of geometric dimension.