In this paper, a hybrid use of response surface approximation methodology and direct optimization method is utilized to design the lightweight and support point layout of the primary mirror. Taking the ultra-low expansion primary mirror of a 2.5 m ground-based optical telescope as an example, the parameter sensitivity analysis of this method, the global optimization of multi-objective genetic algorithm based on Kriging response surface, the local optimization process based on the gradient algorithm of the mixed-integer sequential quadratic programming are studied, and the evaluation function is formulated using the compromise programming theory. The results of integrated optimization show that, compared with the solid mirror of the same size, the lightweight rate is 72.13% when the primary mirror adopts a partially open hexagonal hole sandwich structure on the back. The primary mirror adopts 54-point whiffletree passive support in the axial direction. The root mean square of the mirror surface deformation under the vertical optical axis and gravity load is 6.08 nm, and all indexes meet the design requirements.