This paper includes the investigation of the soil–structure interaction (SSI) effect on the seismic response of 20 and 30-story reinforced concrete moment resisting frames (MRFs) rested on a piled raft foundation using the direct approach. After that, a study is conducted to show the impact of using a cellular raft instead of the designed solid raft on the dynamic response of the building. A study is introduced to select the best gap size for the cellular raft. The soil model is assumed as a single layer of sandy clay. Time history analysis by the direct integration method is performed under seven earthquake records (El-Centro, Northridge, Kobe, Chichi, Friuli, Kocaeli, and Loma), which are scaled to the Egyptian Code for Loads (ECP-201) response spectrum using a full 3D model by a finite element software named (Midas GTS NX). It is concluded that considering SSI significantly affects the dynamic response of high-rise buildings, and using cellular rafts generally leads to a decrease in their dynamic response.