Octadecylamine (OCT) as an alternative for diphenyl guanidine (DPG) in silica-reinforced NR tire compounds with bis-(triethoxysilyl-propyl)tetrasulfide (TESPT) as silane coupling agent was investigated with focus on the improvement of compatibility between the silica surface and rubber molecules, by taking the amine-free rubber compound as a reference. The quantity of OCT and DPG was varied in a range of 2.4–9.5 mmol per 100 parts of rubber by weight (i.e., 0.5–2.5 phr). Bound rubber contents, changes in heat capacity (ΔCp), and immobilized polymer layer (χim) data prove an enhanced interfacial compatibility as the amines are absorbed on the polar silica surface and catalyze the silanization reaction. Comparing the two different amine types, the rubber compounds with OCT show higher interfacial compatibility than the ones with DPG, because of an additional shielding effect promoted by the long alkyl chain that leads to more hydrophobicity. Thus, the rubber compounds with OCT show higher physically bound rubber contents and consequently higher total bound rubber, a higher immobilized polymer layer, as well as a lower Payne effect. However, the compounds with OCT show a higher flocculation rate constant because the physical interactions between amine and silanol groups decrease under thermal treatment. The compounds with OCT show a lower cure torque difference that indicates a lower crosslink density, but because of the good interfacial interaction combining both chemical and physical interactions, the vulcanized rubber with OCT at optimum loading shows better mechanical properties and tan δ at 60 °C when compared with the DPG counterpart. At high (excessive) loading of amines, the compounds with DPG clearly have higher crosslink density and thus higher modulus as well as tensile strength compared with the use of OCT.