In this paper, the mixed refrigeration cycle of Skikda APCI (Air Products and Chemicals Inc.) process in Algeria was studied thermodynamically in order to determine the optimal operat-ing conditions. The energy and exergy balance equations for each process component were es-tablished. The distribution of the exergy destruction of the basic cycle equipment revealed that the compressors had the highest exergy destruction rate. The effects of operating conditions on performance coefficient of the cycle (COP) and exergy efficiency of the APCI process were evaluated; mainly the inlet temperature of the compressors, natural gas (NG) temperature af-ter cooling in the main cryogenic heat exchanger (MCHE) and inlet temperature of the mixed refrigerant (MR) expansion valve. The results of the numerical simulation validated using Aspen HYSYS software indicate that the COP and exergy efficiency of the basic cycle are 2.66 and 59.99% respectively. These results can be improved by reducing the inlet temperature of the compressor and the expander as well as that of the NG after cooling in the MCHE. Finally, the results of the optimization performed using the genetic algorithms (GA) are in agreement with those of the literature. They show signs of improvement in the COP and exergy efficiency of the APCI process by 1.48% and 3.64% respectively compared to the basic cycle.