Compared with conventional natural gas, liquefied natural gas has the advantages of easier storage and transportation, more safety, less indirect investment, better peak regulation, and environmental protection. This paper studies the large-scale cryogenic propane precooled mixed refrigerant (C3MR) liquefied natural gas (LNG) process. The phase equilibrium of the liquefaction process is calculated by the Peng-Robinsonstate equation using ASPEN. A numerical model for the thermal process simulation of the liquefaction process is established by MATLAB. Based on Active X technology, data invocation between software is realized, which overcomes the problem of process variable changes under limited degrees of freedom. The minimum sum of the propane precooling amount for the compressor energy consumption is used as the objective function, the control variate method is used to address the liquefaction process model, and the parameter sensitivity analysis is performed and combined with the exergy analysis. The effects of multiple parameters (e.g., the pressures and temperatures) on the process performance are analyzed and discussed. The results indicate that the combined analysis of the parameter sensitivity and exergy adopted in this paper are able to increase the system performance and reduce the exergy loss of equipment. The maximum reduction of the throttling loss of the process is 60.14%, and the total exergy loss is reduced by 25.8%.