The finite difference method and the volume of fluid (VOF) method were used to develop a three-dimensional numerical model to study wave interaction with a perforated caisson.The partial cell method was adopted to solve this type of problem for the first time. The validity of the present model, with and without the presence of caisson structures, was examined by comparing the model results with experimental data. Then, the numerical model was used to investigate the effects of various wave and structure parameters on the wave force and wave runup of the perforated quasi-ellipse caisson. Compared with the solid quasi-ellipse caisson, the wave force on the perforated quasi-ellipse caisson is significantly reduced with increasing porosity of the perforated quasi-ellipse caisson. Furthermore, the perforated quasi-ellipse caisson can also reduce the wave runup, and it tends to decrease with the increase of the porosity of the perforated quasi-ellipse caisson and the relative wave height.