The multi-effect distillation (MED) desalination is one of the successful desalination technologies. In this paper, a backward MED process for high-salinity wastewater desalination is performed. Also, mathematical models are established based on the energy and mass analysis of evaporator, condenser and flashing chamber. The high salinity wastewater from a typical refinery located in northwest of China was as the research object, and the effects of effect numbers, feed steam, evaporator temperature in last effect and concentration ratio were analyzed concretely to achieve high-salinity wastewater reduction with lower costs. The results indicated that the effect numbers is very important to keep the balance between lower costs and more distillated products in the MED system. More distillated products could be produced with high effect numbers than those with few effect numbers. Also, higher effect numbers led to higher capital costs and distillated product costs. The total heat transfer areas of the whole system reduced obviously with the increase of the feed steam temperature. The GOR value could increase gradually by the increase of evaporator temperature in last effect. When concentration ratio was less 100, the quantity of out brine decreased significantly with the increase of concentration ratio, but further increase of concentration ratio resulted in both slight increase of the quantity of out brine, and the higher concentration of out brine.