Abstract: Minimizing the work consumed in refrigeration system is the most effective measure to reduce the cost of products in sub-ambient chemical processes. The introduction of mixed working fluids into refrigeration system in place of pure working fluids is a recent advancement applied in the field. Due to the lack of systematic design method for Mixed Refrigerant Cycle (MRC), conventional approaches are largely trial-and-error, and therefore, operations might be far away from Optimal operating conditions. In this paper, a novel method for systematic design of MRCs with a given configuration is presented. It combines the benefits of thermodynamics approach and mathematical optimization. An ethylene process was chosen as a typical example of low temperature process. The simulation results show that MRCs can improve the thermodynamic performance of refrigeration system in the case of using Optimal operating conditions and also proper arrangement of the cycle components (cycle configuration).