Abstract: In order to study the optimal system operation schemes and control strategy of high-tech industrialization demonstration project for seawater desalination in Shandong Province, a mathematical model which reflects correctly and comprehensively the system characteristics is an important prerequisite. This paper introduced a mathematical model based on the thermal performance analysis of the system with hybrid desalination method suitable for low temperature nuclear heating reactor, including low temperature multi-effect distiller (LT-MED-TVC) and reverse osmosis (RO) systems, and showed the calculated results of the system operation under different conditions. By comparing with the engineering design parameters and commercial software calculation results provided by RO plant supplier, it is indicated that the model can correctly catch desalination system operating characteristics, and meet the need for further research.