In order to study the effect of Hericium erinaceus polysaccharide (HEP) on the immune and antioxidation functions of immunosuppressed mice. The control group received distilled water orally, the model and experimental groups I, II and III received 0, 80, 160, 320 mg/kg HEP respectively for a fortnight after re-moulding with CTX. Compared with the control group, the secretion of IL-2, IL-4, and IFN-γ, the activity or content of T-AOC, T-SOD, GSH-PX, and the expression of PCNA mRNA in the thymus and spleen were reduced in immunosuppressed mice (P < .05 or P < .01). Compared to immunosuppressed mice, the levels of IL-2, IFN-γ and GSH-PX and the PCNA mRNA expression of spleen and thymus were increased (P < .05 or P < .01), and the microstructure were also obviously improved in the experimental group III. Overall, 320 mg/kg of HEP significantly improved the immune and antioxidant functions.