The evaluation of the compression behavior of the cushioning material is of importance to achieve appropriate packaging design. In order to change packaging design from polymeric-based to more eco-friendly cellulose-based nire effectively, comparative study on the compression behavior between these two packaging materials is crucial. In this study, the stress-strain behavior, hysteresis loss, and response characteristics for cyclic loading were analyzed through compression tests on multi-layered corrugated structure (MLCS) and expanded polystyrene (EPS) packaging materials. MLCS produced in Korea is produced by winding a certain number of single-faced corrugated paperboard, and the compression behavior of this material was turned out to be 6 stages: elastic stage, first buckling stage, sub-buckling stage, densification stage, last buckling stage and high densification stage. On the other hand, EPS’s compression behavior was in 3 stages: linear elastic stage, collapse plateau, and densification stage. The strain energy per unit volume (strain energy density) of MLCS did not differ depending on the material thickness, but it showed a clear difference depending on the raw material and flute type. Hysteresis loss of MLCS ranged from 0.90 to 0.93, and there were no significant differences in the raw material and flute type. These values were about 5 to 20% greater than the hysteresis of the EPS (about 0.78 to 0.87).