Considering the structure preforated by fragments, the dynamic response of the plane sandwich with pre-formed holes under blast loading was investigated by employing the numerical simulation. The numerical models based on structural parameters have been established. The structural dynamic response process has been divided into three specific stages and the deformation modes have been classified and discussed systematically. Based on this, the effect of the number of pre-formed holes on the structural dynamic response has been investigated. It is concluded that the radial kinetic energy of the pre-formed holes resulted from rarefaction wave obviously decreases the vertical displacement of the structure, and the increasing of the number of the pre-formed holes changes the 2D face bearing capacity to 1D beam bearing capacity, to increase the vertical displacement and obviously decrease the bearing capacity. The research results provide a foundation for the analysis of the dynamic structural response and vulnerability of the sandwich structure with pre-formed holes under blast loading, and also provide a reference for the design of sandwich structure protection.