In this work, experimental and mathematical substantiation of the possibility of using the new RCTU-4 hydrophobic catalyst [0.9 mass % Pt/styrene and divinylbenzene (SDVB)] in the separation of protium-tritium isotopic mixtures by a two-temperature catalytic exchange method in a water-hydrogen system was carried out. Variation of the synthesis parameters of the support and the catalyst allowed a significant increase in the activity (≥50 s–1) and heat resistance (≈550 K) of the investigated sample compared to the previously used catalyst RCTU-3SM (kexp = 12 s−1; heat resistance = 388 K). The mathematical model presented in the paper considers three phases (liquid water, steam, and hydrogen gas) and allows optimization of dual-temperature installations in the water-hydrogen system for any isotopic mixtures.