The wave-structure interaction for surface-piercing bodies is a challenging problem in both coastal and ocean engineering. In the present study, a two-dimensional numerical wave flume that is based on a newly-developed meshless scheme with the generalized finite difference method (GFDM) is constructed in order to investigate the characteristics of the hydrodynamic loads acting on a surface-piercing body caused by the second-order Stokes waves. Within the framework of the potential flow theory, the second-order Runge-Kutta method (RKM2) in conjunction with the semi-Lagrangian approach is carried out to discretize the temporal variable of governing equations. At each time step, the GFDM is employed to solve the spatial variable of the Laplace’s equation for the deformable computational domain. The results show that the developed numerical method has good performance in the simulation of wave-structure interaction, which suggests that the proposed “RKM2-GFDM” meshless scheme can be a feasible tool for such and more complicated hydrodynamic problems in practical engineering.