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Floating Liquefied Natural Gas (FLNG) facilities have limited space available and a high possibility of accidents occurring. The severity of consequences requires an inherently safer layout design. Scope of the liquefaction process requires to determine the size of utilities, operating costs, the deck area and the number of LNG trains. The layout of the liquefaction process plays a key role in defining operational and economical safety of the whole FLNG plant. The present study focuses on developing a novel methodology to design an inherently and optimally safer layout for the generic multi-deck liquefaction process of an FLNG plant. The integrated inherent safety principle is applied at the early phases of the layout design considering inherent safety and cost indices in three different layout options, and for the final design the most optimal option was selected. The proven indexing approach quantified the associated risks in all units. Safety measures were undertaken to eliminate or reduce the risk to an acceptable level. The results showed that the economic losses due to domino effects were limited by an improved layout design and passive control strategies. This study only dealt with evaluation and analysis of critical units of the plant due to a lack of detailed information at the early phase of the design. However, the proposed method plays a positive role in obtaining an inherently safer layout design of any multi-deck plants.