The panel cavity structure is one of the key components of the aircraft (vehicle) body and is among the main noise transmission pathways. Based on the modal superposition and Galerkin method, this paper realizes the theoretical model of sound insulation of the clamped, double-panel structure. The non-dominated sorting genetic algorithm-II (NSGA-II) is used to realize the sound insulation of the clamped double-panel structure. Through optimization, the fitting function and law of structural surface density and the optimized normal weighted sound insulation Pareto fronts were obtained. The results show that among the optimization, for the Pareto front cases, their double-panel thickness ratio h1/ h2 is relatively far away from 1, and the corresponding cavity thickness H is relatively large. The influence of boundary conditions and size effects of lightweight sound insulation optimization are also discussed. The research on the influence of boundary and size indicates that the difference in the optimal weighted sound insulation Pareto fronts corresponding to the same surface density is mostly within the 1 dB range. Both the boundary and thickness of the panel will affect the frequency STL, while the boundary conditions or structure size changed, even the total thickness of panels needs to be the same, and the structure can also have similar weighted sound transmission loss ( Rw) when the thickness ratio of the double-panel structure is chosen properly. The difference of material effects is also discussed. This research provides a method for the sound insulation optimization of clamped double-panel structures concerning the boundary and size effect.