The interaction between a shock wave and solid particles involves complex gas–solid two-phase flow, which is widely used in industrial processes. Theoretical analysis, an experimental test, and simulation were combined to investigate the interaction process between a shock wave and quartz sand particles. The variation of physical parameters of the two phases during the interaction process was considered theoretically. Then, a novel vertical shock tube generator was employed to record the pressure attenuation and dispersion process of solid particles. Finally, the complex gas–solid two-phase flow was simulated based on the computational fluid dynamics method. The results showed that a nonequilibrium state was formed during the interaction process and momentum exchange generated, resulting in a drag force of the shock wave on the particles. The shock intensity obviously attenuated after the shock wave passed through the solid particles, and this part of the energy was work on the solid particles to drive their dispersion. A three-dimensional annular vortex was generated around the solid particles due to the entrainment effect of airflow. Under the shock wave action of 1.47 Ma, the three types of solid particles with average diameters of 2.5, 0.95, and 0.42 mm presented different motion laws. The particles with smaller size were easier to disperse, and the cloud that formed was larger and more uniform.