To satisfy the worldwide demand for energy, the liquefied natural gas (LNG) industry has grown significantly in the past three decades owing to its low CO2 emissions and high thermal efficiency compared to the other available energy resources. However, the process of natural gas liquefaction is generally considered to be energy-intensive. In this context, a novel hydrofluoroolefin (HFO-1234yf)-based mixed refrigerant, with the advantages of zero ozone depletion and minimal global warming potential, is proposed to liquefy natural gas in an ecological and energy-efficient manner. A new liquefaction cycle using the HFO-based mixed refrigerant is developed to fully utilize its potential. The results reveal that the overall energy requirement for natural gas liquefaction can be reduced by 46.4% compared with a single mixed refrigerant process, 42.5% compared with a dual mixed refrigerant process, and 36.3% compared with the Linde-single mixed refrigerant process. Economic analysis based on the capacity parameters of each equipment is also performed to emphasize the commercial feasibility of the proposed LNG process. The proposed HFO-based mixed refrigerant system provides an innovative solution to improve the ecological aspects and energy efficiency of natural gas liquefaction processes. (C) 2018 Elsevier Ltd. All rights reserved.