The work aims to discuss the effect of cell defect distribution location and its size on the in-plane cushioning property of regular hexagonal honeycomb cores (RHHCs). Based on the finite element analysis software Ansys/LS-DYNA, a reliable dynamic calculation model of RHHCs under the action of in-plane dynamic compression load was established, and the velocity of dynamic compression was below 100 m/s. Evaluation indicators of cushioning property were obtained by further analysis on the computed results. There were six kinds of cell defect distribution locations in the specimens because of their symmetry. The effect of the defect size was studied in the case of missing cell clustering in the center of the specimen. The cell defect reduced the value of densification strain for the intermediate/low-velocity impact and increased such value of the RHHCs for the high-velocity impact. With the increase of cell wall thickness, the influence of defect location on the dynamic peak stress first increased and then decreased. The cell defect made the energy absorbed per unit mass show the trend of being less after being greater than the complete honeycomb unit mass energy which was increasingly obvious with the increase of velocity. At low-velocity impact, the value of the energy absorbed per unit mass decreased significantly with the increase of the number of missing cells for any defect type. Compared with the cell defect distribution location, its size has a greater effect on the in-plane cushioning property of RHHCs.