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Gantries and beams, as the main load-bearing structures of heavy equipment, usually belong to the box structure consisting of outer walls and inner stiffened plates. The structure of the stiffener layout is bulky due to empirical design, leading to higher material consumption and impacting mechanical performance. There are challenges in effectively identifying load-transferred paths within 3D box structures through direct topological optimization. A method for optimizing the layout of internal stiffened plates of large box structures based on load paths is proposed in this paper. Initially, based on the load conditions acting on the structure, the 3D box structure is decomposed into 2D functional sections. Subsequently, the load paths on the functional cross-section are visualized according to the load path method. Finally, the stiffener layout of the ultimate optimized structure is designed according to the effective load path distribution. Taking the gantry of a heavy-duty aluminum ingot composite processing unit as an example, the optimization results indicate that the maximum stress of the structure decreased by 14.9%, the maximum deformation reduced by 32.95%, and the overall weight decreased by 14.4%. This demonstrates that the approach proposed in this paper is practical and effective for optimizing stiffener layouts in large-box structures.