Abstract: Through LS-DYNA finite element simulation software, the shock wave propagation law and structural damage of the blast-resistant chamber subjected to the explosions exceeding 100 kg TNT equivalent were studied. The air pressure distribution and peak overpressure variation across horizontal and vertical sections were analyzed, the propagation law of shock wave was discussed, and the influence of different parameters on the failure mode of blast-resistant chamber was studied. Three damage indexes based on the bearing angle were proposed: λ (the ratio of the upward bending chord length to the top cover length), η (the ratio of the spalling area of the wall panel to the surface area), μ (the ratio of the bending radius of the top cover to the half span) to evaluate the damage degree. The results showed that the peak overpressure near the rear wall area was significantly higher than that of the explosion venting surface. Increasing the thickness of wallboard and concrete strength could change the failure mode from shear failure to flexural failure, while variations in reinforcement ratio and steel yield strength had minimal impact on the failure mode but enhance shear and flexural capacity. Design recommendations include a minimum wall thickness of 300 mm, concrete strength ranging from C30 to C40, and steel yield strength between 235 MPa and 400 MPa. Based on the damage results, the location of the test stand within the chamber should meet the structural requirement of being positioned between the venting surface and the mid-plane of the chamber.