In order to investigate the dynamic response, damage evolution and failure of concrete tunnel structure by underwater explosion load, laboratory tests and numerical calculations are adopted in this paper. Firstly, a 40∶1 specimen was designed according to the East Lake underwater tunnel. An explosion test of the underwater box concrete tunnel model was then carried out. The dynamic response rule of the concrete specimens under different emulsion explosive equivalent was compared by monitoring the strains. Meanwhile, the failure forms of the scaled model of the box tunnel caused by the underwater blasting load were investigated by measuring the size of the failure range and the length of crack propagation. Furthermore, a 1∶1 modeling simulation analysis of the test was carried out using the S-ALE algorithm in ANSYS/LSDYNA. It is found that the simulation results were basically consistent with the experimental results by comparing the experimental data and failure patterns. At the same time, the complete propagation process of the underwater explosion shock wave and the deformation law of the specimen structure were obtained by further analysis of the simulation results. Finally, the dynamic response mechanism of the box tunnel specimens under explosion load was revealed through statistical analysis of strain and displacement data at the measuring points. The results show that the transverse strain of the box concrete tunnel structure is much larger than the longitudinal strain. The failure location of the tunnel is mainly concentrated in the area near the explosion source and the structural angle position. It is verified that the S-ALE algorithm can simulate the dynamic response and damage evolution of the structure by underwater explosion accurately.