Facility layout is a very important part in the design of a plant, a good layout can greatly reduce the cost of the plant construction and operation, which brings considerable benefits to the investors. Previous researches on facility layout problems mainly focus on arranging facilities in a single frame, however, facilities are placed in several frames rather than stacked together in an actual process unit. In this work, facilities are arranged in terms of frames and the coupling of frame scale and facility scale is studied, which makes changes in traditional layout researches. Both the frame location and the facility location in the frame are optimised by minimising the total cost. The safety distance and the fire protection distance of facilities are considered. The algorithm combining genetic algorithm and surplus rectangle fill algorithm is adopted. The objective function is the sum of the pipeline construction cost, material handling cost, land cost and floor construction cost. The impact of the key connections of high temperature is also considered to make the result layout closer to reality. The mathematical model is calculated in MATLAB. In case study, a catalytic cracking unit with 217 facilities and 245 material flows is modelled. In the process of optimisation, the ideas of multiple frames and key connections are fully addressed. As the result shows, 16 % reduction of the total cost and the locations of frames and facilities are reached, which indicates that the proposed method can acquire a reasonable facility layout, and the frames make the final layout closer to the actual situation.