Based on the proteomic analysis of the CSF samples obtained from children with HEV-positive meningitis, we found that a large number of upregulated proteins in the CSF, including C2, C9, C4B, C1RL, ADIA, LAIR1, ADIB, C1R, VCAM1, ADA2, SERPINA1, C5, CD14, SPP1, epididymal secretory sperm binding protein, ICAM2, and IGHV2–26, were related to complement and coagulation cascades, NF-kappa B signaling pathway, and toll-like receptor signaling pathway. The gene discussed is C4B; the disease is meningitis.