Hydraulic interactions between tsunami flow and structures located along coastlines include quite complex phenomena, because the tsunami flow acts on a structure with trapping air. In order to design structures such as an evacuation building properly, it is important to consider the effect of this entrapped air in the investigation of tsunami hydrodynamic loads. This study is aimed at investigating the characteristics of tsunami hydrodynamic loads on multi floor buildings with openings by using a two-phase flow model in a three dimensional space. Two types of building models, the building with openings and the building without openings, were examined in this study. Numerical results were compared with the results obtained from one-phase flow simulations, and also verified with the experimental ones. The numerical results obtained from the two-phase flow model show good agreement with the experimental results. Furthermore, the two-phase flow model simulates the interface between water and air inside the building more accurately than the one-phase flow model. The openings in the building reduce the sustained pressure acting on the front side. The effects of the opening ratio and entrapped air to the wave pressures and uplift forces acting on the floor slab were also discussed.