The propane precooled mixed refrigerant (C3MR) process is the most used technology for liquefying natural gas and has been widely studied. For large scale LNG plants, the mixed fluid cascade (MFC) process is emerging as a novel solution and needs to be thoroughly investigated. There is limited data on the economic aspects, and energy consumption of MFC, as well as its performance in comparison with C3MR. Several operating and design parameters govern the performance of the liquefaction process and careful optimization is required. This paper presents a thorough comparison between the C3MR process and the MFC process. Aspen Hysys is used to simulate the processes under the same conditions of precooling, liquefaction and subcooling. The process operating and design conditions are further optimized using the genetic algorithm. The objective functions employed for the optimization consider the equipment cost (CAPEX) and the operating cost (OPEX) for a more representative solution. Finally, energy consumption, capital cost, operating cost and annual cost are discussed selecting the most suitable process for the natural gas feed analyzed.