This paper presents a study on three-dimensional seismic soil-structure interaction analysis of a piled-raft (PR) foundation in clay by the substructure approach. Two different pile modeling techniques were adopted and compared with centrifuge shaking table test results reported in the literature. The effect of pile spacing on dynamic impedances, kinematic response parameters, axial pile forces and bending moments of PRs is studied. It is found that the presence of a rigid raft on a pile group results in significant variation in vertical and horizontal dynamic stiffness after a dimensionless frequency (ao) value of around 0.22. The influence of raft on kinematic response parameters at the top of raft is found to be significantly influenced by pile spacing beyond a dimensionless frequency (ao) value of 0.4. The axial forces generated at the pile heads of a PR-structure system during seismic shaking are quantified using a new dimensionless factor, and are found to be significantly influenced by the pile spacing. Pile layout in the PR system is found to play an influential role in seismic response as well as pile bending moment for a structure-PR-soil system studied. © 2019 World Scientific Publishing Company.