In order to accurately predict the on-wave resistance and responses to hull motions of ships in actual sea conditions, the k-ε method of the RNG model is adopted on the basis of the unsteady RANS method. The twoformula turbulence model deals with the viscous flow, the VOF method captures the free surface, the velocity boundary method makes waves, the artificial damping method is used to eliminate waves, and the nested grid technology is used to deal with the motion response of ships on waves. Combined with the 6-DOF motion formula, a three-dimensional numerical wave cell for regular waves is established. For one example, taking a KCS Container ship and fishing boat sailing at a mid-high-speed, the increase of wave resistance and motion response at different wavelengths are analyzed, and the simulation results are compared with the experimental value, the content of strip theory in potential flow theory and the panel method to prove the reliability of CFD method in predicting ship motion.