A series of numerical simulations were conducted to clarify the shock–structure interaction inside an inner-grooved straight tube and the mitigation effect of the groove structure on the expansion of the blast wave at the exit. The results showed that the periodic grooves of the groove structure generate multiple reflected shock waves. Each time a shock wave reaches a groove, some of the shock wave and gas flow behind it propagates directly through the downstream groove, and the rest is reflected to the upstream groove. This splitting decreases the shock wave strength inside the tube. To clarify the blast mitigation effect of the configuration of the groove structure, parametric studies were conducted that changed the height and interval of the periodic grooves. The flow characteristics inside the tube were analyzed to understand the blast mitigation efficiency of the groove structure. The groove height had a significant impact on the blast mitigation efficiency, and the optimal interval for maximum blast mitigation efficiency depended on the groove height. The total energy release rate from the tube exit is a characteristic value of the blast wave strength at the exit, and it can be used to scale the blast wave strength outside.