Moonpools protect objects from the influence of environmental loads to some extent, however, the influence of the moonpool on floater motion is complicated. Based on the validation of CFD (computational fluid dynamics) simulations against model tests, the motion responses of a conceptually designed semi-submersible platform with a hollow annular cylindrical moonpool are analyzed under waves in a 100-year return period, which is the design condition. The results show that a larger opening size and a smaller moonpool chamber can decline the hydrodynamic responses of heave and pitch of the platform. Apart from wave frequency in the heave frequency, obvious low frequency is found, which is related to the difference frequency between the incident wave frequency and natural heave frequency. This complex heave motion is attributed to the moonpool shape. The vorticity analyses show that the large damping due to flow separation in the proximity of the bottom edge of the moonpool is beneficial for inhibiting the piston-like motion in the moonpool, resulting in reduced pitch motion but increased heave motion. Finally, an optimal design in terms of the heave motion is suggested with care owing to the vigorous piston-like motion in the moonpool for design cases.