In this paper, cycle performance analysis of two-stage compression and two-stage expansion refrigeration system using Natural refrigerants is presented to offer the basic design data for the operating parameters of the system. Alternative natural refrigerant R290(Propane), R600(Butane), R717(Ammonia), R1270(Propylene) for freon refrigerant R22 were used working fluids in this study. The operating parameters considered in this study included evaporation temperature, condensation temperature, subcooling degree, superheating degree, and mass flow rate ratio of inter-cooler. The main results were summarized as follows : The COP of two-stage compression and two-stage expansion refrigeration system increases with the increasing subcooling degree and mass flow rate ration of inter-cooler, but decreases with the increasing evaporating temperature, condensing temperature and superheating degree. Therefore, subcooling degree, mass flow rate ratio of inter-cooler of two-stage compression and two-stage expansion refrigeration system using alternative nreon refrigerants have an effect on COP of this system.