The interaction between soil and structure, known as Soil-Structure Interaction (SSI), plays a crucial role in the design and analysis of reinforced concrete (RC) structures, particularly in seismic-prone regions or areas with varying soil conditions. This study investigates the effects of SSI on an RC frame building with pile foundations, considering three different soil types: hard, medium, and soft. To simulate the behavior of the soil in the static loading condition the Mohr-Coulomb model was used and finite element program ANSYS was used for the analysis. The results of the vertical reactions, the horizontal reactions and the bending moments at the foundation level, that is at corner, edge and central pile locations, are investigated with respect to the SSI occurrences. The results show that the soil type has highly significant effect on the structural response. The vertical reactions at corner, and edge piles in soft soil increased due to increased settlement and load redistribution; central piles had lower vertical reaction. As a result of the low stiffness and high compressibility of the soft soil that amplifies lateral forces and moments and reduces vertical reactions, horizontal reactions and bending moments were highest for soft soil and particularly for edge piles. On the contrary, the fixed base model without SSI under predicted these reactions and moments, implying the shortcomings of conventional design that omit soil flexibility. The study shows that SSI should be included in the RC structure design, particularly in soft soil conditions, to give accurate prediction of structural behavior and avoid risk of excessive settlement, lateral deformation and foundation rotation. These findings are practical and impart pile foundation design with practical consideration and highlight the need of specialized design approach depending on the soil conditions in order to improve structures’ safety and stability. Both normative and empirical contributions to the SSI literature are made by this research, and recommendations for improving the performance of RC structures in different soils are given to the engineer.