Reverse electrodialysis (RED) is a promising technology to extract electric energy from salinity gradient energy (SGE). Through being combined with multi-effect distillation (MED) where low grade heat is converted into SGE, a closed-loop system named hybrid MED-RED power generation system was presented. In this study, a detailed thermodynamic analysis for the system was performed to investigate how the relevant operation and structure parameters influence on the performance of the system. When hot and cooling water temperatures were respectively 80 degrees C and 20 degrees C and a six-effect distiller was applied, the energy conversion efficiency of the system reached 0.76% under the given operation conditions. The results showed that the increase of the hot water inlet temperature, initial salt molarity of brackish solution and effect number of MED all would positively influence on the performance of the system. The energy conversion efficiency of the system could be promoted to 0.85% when the hot water inlet temperature and initial salt molarity of brackish solution were 95 degrees C and 3.75 mol.kg(-1) respectively. In addition, under the given operation conditions, when the effect number of MED reached 10, the energy conversion efficiency of the system could reach to 1.01%.