To investigate value of amplitude-integrated electroencephalograph (aEEG) in early diagnosis and prediction of long-term prognosis of neonatal hypoxic-ischemic encephalopathy (HIE), 120 HIE Children were randomly assigned into aEEG group and control group (n = 60 per group). Children in each group were sub-divided into mild, moderate and severe HIE groups (n = 20 per group). 1, 3, 14 and 28 days after birth, aEEG was performed in aEEG group; 3, 14 and 28 days after birth, neonatal behavioral neurological assessment (NBNA) was done in both groups. Children who discharged were followed up at adjusted gestational age of 12 months with Denver Developmental Screening Test (DDST) and prognosis evaluation. Results: aEEG manifestation was positively related to clinical severity of HIE (r = 0.843, P < 0.01). On day 3 and 14, NBNA score was comparable between two groups (P > 0.05), but significant difference in NBNA score was noted on day 28 (P < 0.05). On day 3, 14 and 28, aEEG manifestation was positively associated with prognosis at adjusted gestational age of 12 months (r = 0.832, 0.857, 0.778, 0.743, P < 0.01). In aEEG group, disability rate was 13.8%, which was significantly lower than that in control group (23.2%); cure rate in aEEG group (60%) was significantly higher than that in control group (40%). Moreover, long-term prognosis was also dramatically different between aEEG group and control group (χ2 = 4.107, P < 0.05). Conclusion: aEEG manifestation is significantly associated with clinical severity of HIE and may be helpful for early diagnosis of HIE. aEEG may be used to predict long term prognosis of HIE children.