The layout of the existing complex operation interface lacks quantification of human comfort. Based on this, the work aims to propose a method for optimizing the layout of operation interfaces that quantifies human comfort factors. The comfort requirements of the operation interface were quantified through rapid upper limb assessment and visual attention evaluation, and a mathematical model for optimizing the layout of human comfort factors was established based on the importance of the components to be laid and the weight of usage frequency. Then, the quantum particle swarm optimization algorithm was adopted to solve the mathematical model, and the operation interface was laid out based on the solution results. Finally, the fuzzy comprehensive evaluation method was used to compare the operation interface design schemes before and after optimization. The layout design of a certain type of mining excavator operation interface was validated as an example, and the comfort of the optimized operation interface was significantly improved. This study can provide a layout optimization method for complex operation interfaces with the main objective of human comfort factors.