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Facility layout is widely used in manufacturing system. It has a very important effect on the performance of manufacturing system. The three types of facility layout, including linear, U-shape, and semi-circular layout are introduced firstly. Based on the lower selling price of customers' demand, the components of manufacturing cost are analyzed secondly. Then the relationship between the manufacturing cost and objectives of facility layout are described. Meanwhile, the mathematical and simulation models related to several parts of manufacturing cost of facility layout are set up respectively. Finally, the simulation of these models for three types of facility layout is running in QUEST. After analyzing the simulation results, conclusions are obtained: (1) material handling cost of loop layout is lowest among the three types of facility layout; (2) area utilization rate of loop layout is higher than the others; (3) equipment and labor utilization of U-shape layout is the higher than others in the same moment. This research results will provide the references in selecting the type of facility layout based on manufacturing cost.