<p>Improving frame stiffness is essential for improving the forming accuracy of large heavy-duty presses. The current method of designing the frames mainly relies on manual experience, and the stiffness of the frame can only be verified at the final stage of manufacturing, which is very inefficient and with poor reliability. In this study, we propose an high efficient structural design method integrated simulation-optimization-verification (HESD-SOV) for improving stiffness of large heavy-duty press frames. The HESD-SOV method integrates finite element analysis for deformation assessment, topology optimization using the variable density method, local structural optimization and experimental verification. Experimental tests demonstrate that the redesigned frame’s weight is reduced by 26.4 % and its stiffness increased by approximately 40 %. These advancements, along with improved manufacturability, validate the effectiveness of the HESD-SOV method. This research presents a practical and high efficient solution for structural optimization of the heavy-duty presses frame with high stiffness.</p>