According to the current actual situation of nuclear industry and environmental protection requirements, the nuclear energy industry has an increasingly strong demand for high hydrogen isotope enrichment separation. In this study, a thermodynamic steady-state simulation model was established for the enrichment and separation process of deprotium by low temperature distillation with moderator, and the ionization equilibrium reaction process of H2O-D2O-DHO was innovatively considered. By comparison, it is proved that the model established in this study, including physical property selection, regression and prediction of missing physical property data, is scientific, reasonable and feasible. On this basis, the optimum operating parameters of low temperature enrichment distillation technology for tritium removal by moderator are determined by sensitivity. This study provides theoretical guidance for the research ideas and in-depth research of low temperature enrichment distillation technology for tritium removal from heavy water.