Wave run-up is an important phenomenon that should be considered in ocean structure design. In this study, the wave run-up of a surface-piercing circular cylinder was calculated in the time domain using the three-dimensional linear and fully nonlinear numerical wave tank (NWT) techniques. The NWT was based on the boundary element method and the mixed Eulerian and Lagrangian method. Stokes second-order waves were applied to evaluate the effect of the nonlinear waves on wave run-up, and an artificial damping zone was adopted to reduce the amount of reflected and re-reflected waves from the sidewall of the NWT. Parametric studies were conducted to determine the effect of wavelength, wave steepness, and the draft of the cylinder on the wave run-up of the cylinder. The maximum wave run-up value occurred at 0°, which was in front of the cylinder, and the minimum value occurred near the circumferential angle of 135°. As the diffraction parameter increased, the wave run-up increased up to 1.7 times the wave height. Furthermore, the wave run-up was 4% higher than the linear wave when the wave steepness was 1/35. In particular, the crest height of the wave run-up increased by 8%.