Abstract Density functional theory was used to study the interfacial interactions between clay and polymer in polymer/clay nanocomposites, with a focus on nylon 6 matrix. The binding energy and the distance between nylon 6 and clay surface were predicted. The effect of the isomorphic substitution in clay octahedral and tetrahedral layer on the strength of the interfacial interactions was also examined. The interaction strength between nylon 6 and clay surface was found to increase with the degree of isomorphic substitution. And the magnitude of the binding forces, reflected from the calculated binding energies, was found to be higher when the substitution took place in tetrahedral layer (e.g., Al 3+ for Si 4+ ). No covalent bonds were observed between nylon 6 and the clay, which means that the chemical structures of the clay and nylon 6 are unchanged during the mixing process.