In this study, the structure characteristic of the Hericium erinaceus polysaccharide (HEP) was investigated using Fourier transformed infrared spectrometry (FT-IR), gas chromatography-mass spectrometry (GC-MS), gel permeation chromatography (GPC), methylation and nuclear magnetic resonance (NMR). The results showed that HEP, with a molecular weight of 43 KDa, was mainly composed of glucose and rhamnose. The linkages of the sugar residues of HEP were → 6) β-d-Glcp-(1 → and → 2) -α-l-Rhap-(1 → residue at the end of the branches. The Fusarium toxin deoxynivalenol (DON)-induced cellular injury model for IPEC-J2 cells was established and used to investigate the protective effects of HEP against the oxidative stress. The results suggest that HEP could significantly protect IPEC-J2 cells from DON-induced oxidative stress, inhibit DON-induced apoptosis and reduce the production of reactive oxygen species (ROS). Overall, this study suggested that HEP could be explored as potential antioxidant agents for DON-induced intestinal mucosa injury.