Liquid phase catalytic exchange (LPCE) is one of the key technologies for tritium removal of tritiated water, such as effluents from Fukushima nuclear power plant. Although former researchers have widely studied this process theoretically, the reported results differ from each other due to different assumptions and parameters adopted. In this work, the principle of Gibbs free energy minimization is applied, with only basic physical properties and no more other assumptions involved. The predictions of isotope exchange are more accurate, and the average error between calculation results and experimental data reduces from 4.45%~6.65% to 2.17%. Then the catalytic exchange behaviors are systematically investigated in the protium-deuterium (H-D) system, and the influence of the cascade processes are emphatically analyzed. The method established in this paper could be applied to catalytic exchange systems for tritium separation, which is essential for the development of water detritiation.