Analyzing the entire liquefaction cycle, using a large temperature span with many degrees of freedom, may not always result in a practical solution. The objective of this paper is to investigate the feasibility of using an environmentally friendly refrigerant compound, ammonia, in the mixed refrigerant (MR) for the liquefied natural gas (LNG) pre-cooling cycle through thermodynamic performance, economic analyses and environmental impact. Fifteen cases studies within three major mixed refrigerants groups of MR-1, MR-2 and MR-3 were developed by adding ammonia to various molar compositions of lighter and heavier hydrocarbons. The thermodynamic analysis shows increasing ammonia’s concentrations in the mixed refrigerant by 10% had the largest enhancement on coefficient of performance (COP) of MR-1 by 0.67 and decreased the specific energy consumption of the pre-cooling cycle by 128 kJ/kg compared to the base case. Economic analyses revealed that the mixed refrigerant MR-1, with ammonia, methane, ethane and propane, benefited the most from higher concentration of ammonia in the mixed refrigerant, which resulted in both lower annual capital and operational costs by $2.52 MM and $3.67 MM, respectively. Lastly, reducing the methane concentration in MR and replacing it with ammonia, decreased the amount of refrigerant leakage through compressor’s seals and reduced the global warming potential index (GWPI) of mixed refrigerant up to 24.3%.