Taking the lightweight optimization of skinned purlin structure in large-scale launch vehicle as the research background, the post-buckling lightweight optimization of large-diameter and large-loaded skinned purlin structure was carried out. In order to achieve ultimate bearing capacity of the structure, the post-buckling behavior of skinned purlin structure was analyzed based on the parametric model established by Python code. Considering that discrete topology and continuous size variables were involved in the lightweight optimization of skinned purlin structure, sequence approximate optimization method based on the surrogate model and combinatorial optimization algorithm was proposed. What′s more, approximate optimal solution was used to accelerate algorithm convergence, which can obtain the final design scheme of skinned purlin structure. The results of engineering examples show that the sequence approximate optimization method propose in this paper make the weight loss effect of skinned purlin structure obvious, and verifies the effectiveness of the method.