Presently, the liquefaction of hydrogen represents a promising solution to alleviate challenges associated with its storage and transportation. It is crucial to formulate methodological frameworks for scrutinizing hydrogen liquefaction routes to enhance energy efficiency. This paper endeavors to establish, assess feasibility, and refine a novel approach for a high-capacity hydrogen liquefaction facility, leveraging the cold energy from liquefied natural gas (LNG). This new route utilizes four hybrid refrigeration systems, each designed to handle 50 × 103 kg daily. Significant energy savings are achievable through the primary utilization of LNG’s energy in the precooling stage and the generation of electrical power during the vaporization phase. The architecture of this novel route is crafted around the principles of energy conservation, incorporating thermodynamic assessments alongside economic and environmental viability studies. Furthermore, the performance of this innovative hydrogen liquefaction method is thoroughly evaluated across both non-optimized and optimized scenarios. Advanced techniques such as composite curve and uncertainty analyses are employed to provide a detailed examination of heat cascades and cost differentials. The findings indicate that managing LNG’s cold energy is crucial for refining the hydrogen liquefaction route, potentially reducing the specific power requirement of the optimum route by 27.4% compared to its non-optimum counterpart. Moreover, in the optimized scenario, there is a decrease of ~4.72% in unit production expenses, 26.26% in CO2 emissions, and 21.85% in specific power usage for avoided CO2 emissions.