The purpose of this study was to explore the clinical features of neonatal HFMD complicated with encephalitis through the comparative analysis of clinical manifestations, CSF routine and inflammatory factor levels (CK-BB, MMP9, UCH-L1), serum immunoglobulin levels (IgM, IgG, IgA), craniocerebral MRI, aEEG, and prognosis of neonatal HFMD complicated with encephalitis. Here, CD40LG is linked to hand, foot and mouth disease.