The thermal dissociation of tri-n-octylamine hydrochloride (TOAHCl) was investigated using both the quantum chemical simulation and experimental methods. The pathway through which a mixture of trin-octylamine (TOA) and hydrogen chloride (HCl), rather than di-n-octylamine (DOA) and 1-chlorooctane,are produced has been determined through transition state (TS) search with Intrinsic Reaction Coordinate (IRC) calculations. Particularly, strong agreement between the experimental FTIR spectra and that of TOA demonstrates the same result for the first time. Moreover, the thermal dissociation of TOAHCl proceeds intwo continuous steps, which is different from the low molecular mass amine hydrochlorides. The experimental enthalpy of the dissociation was 70.793 kJ mol⁻¹ with DSC measurement which is very close to the density functional theory (DFT) calculation result 69.395 kJ mol⁻¹. Furthermore, with the aid of DFT calculations, some other important thermochemical characteristics such as crystal lattice energy with the value of 510.597 kJ mol⁻¹ were evaluated by means of Born–Fajans–Haber cycle.