Abstract: This study aimed to clarify the structural characteristics of Hericium erinaceus Polysaccharides and their protective effects against corticosterone-induced injury in PC12 cells. HEP was extracted and purified from the fruiting bodies of Hericium erinaceus by water extraction-alcohol precipitation and column chromatography. Its component contents were determined using the phenol-sulfuric acid method, Coomassie brilliant blue method, and other techniques. Structural characterization was performed via Fourier Transform Infrared Spectroscopy, ultraviolet full-wavelength scanning, molecular weight determination, Scanning Electron Microscopy, and Congo red assay. A PC12 cell injury model induced by 200 μg/mL corticosterone was established, and the protective effects of HEP were investigated using the CCK-8 assay, Lactate Dehydrogenase release detection, and flow cytometry. The results showed that HEP had a total sugar content of 75.63%, containing 8.35% protein and 7.93% uronic acid, with a weight-average molecular weight of 1.94×10⁴ Da. It possessed a β-D-glucan backbone structure, exhibited a filamentous network arrangement at the microscopic level, and contained partial triple-helix conformations. Furthermore, HEP could dose-dependently increase the viability of damaged PC12 cells (up to 81.28%), significantly reduce LDH release (down to 362.3 U/L), and decrease the cell apoptosis rate (down to 3.77%). In conclusion, HEP exerts a definite protective effect against corticosterone-induced neurocyte injury and can be further studied as a potential functional food component related to antidepressant effects.