Abstract: A finite element analysis of the blast-resistant performance of the aluminum honeycomb sandwich structure was conducted by using the CONWEP calculation model. The maximum deformation of the back plate and the specific absorption energy of the sandwich layer were used as the blast-resistant performance indexes, the benchmark model of the aluminum honeycomb sandwich structure was established according to the composite structure of different matrix materials. Based on the benchmark model, the effects of structural parameters and cell types on the blast-resistant performance of aluminum honeycomb sandwich structure were quantitatively studied. The results show that the composite structure with Al2024T351 for the front plate and RHA for the back plate has excellent blast-resistant performance; compared with the thickness change of the back plate, the influence of thickness change of the front plate on the blast-resistant performance index is more significant. The multi-objective optimization design of the blast-resistant performance of the aluminum honeycomb sandwich structure was done by using the method of building a surrogate model, and the blast-resistant performance of the aluminum honeycomb sandwich structure was obviously improved, which has certain guiding significance for the engineering design of the blast-resistant structure.