This paper focuses on the lightweight design of a 6-DOF (Degree-of-Freedom) heavy-duty industrial robot with the load of 1000 kg. Semi-analytic models, which are built with a clear mathematical format and explicit mechanical implications, result in key performance indices. These indices include end self-weight deformation (ESWD) and low-order natural frequencies (LONF). The optimization function with the thicknesses of its waist and upper arm as optimization variables, as well as with the objective to achieve a structural lightweight design without compromising ESWD and LONF over the workspace is designed. The optimization results demonstrate that the optimized robot can maintain nearly unchanged global indices while reducing weight by approximately 150 kg, thereby validating the effectiveness of the approach employed.