Objective To explore the value of serum DNA methyltransferase(DNMT)1,DNMT3a and brain-derived neurotrophic factor(BDNF)detection in the prognosis evaluation of neonates with hypoxic-ischemic encephalopathy(HIE).Methods From January 2016 to January 2023,84 neonates with HIE diagnosed and treated in our hospital were selected as the observation group,and 84 healthy newborns in our hospital during the same period were selected as the control group.According to the severity of the disease,the patients were divided into mild group(36 cases),moderate group(28 cases)and severe group(20 cases).The serum levels of DNMT1,DNMT3a and BDNF were detected by enzyme-linked immunosorbent assay(ELISA);Factors influencing the prognosis of neonatal HIE were analyzed by multifactor Logistic regression;the predictive value of serum DNMT1,DNMT3a and BDNF levels on the prognosis of neonates with HIE was analyzed by ROC curve.Results Compared with the control group,the levels of DNMT1 and DNMT3a in serum of neonates with HIE in mild,moderate and severe groups in-creased obviously in turn(P<0.05),the level of BDNF decreased obviously in turn(P<0.05);compared with the good prog-nosis group,the serum DNMT1 and DNMT3a levels in the poor prognosis group were obviously higher(P<0.05),and the BDNF level was obviously lower(P<0.05);Multifactor Logistic regression analysis showed that the severity of disease,DNMT1 and DNMT3 a were risk factors affecting the prognosis of neonates with HIE(P<0.05),neonatal Apgar score and BDNF were protec-tive factors affecting the prognosis of neonates(P<0.05);the area under the ROC curve(AUC)of the combined detection of ser-um DNMT1,DNMT3a and BDNF in predicting the prognosis of neonates with HIE was 0.955,which was better than their individual prediction area(Z combined detection-DNMT1=2.046,P=0.020;Zcombined detection-DNMT3a=3.046,P=0.001;Zcombined detection-BDNF=2.073,P=0.019).Conclusion The levels of DNMT1 and DNMT3a in serum of neonates with HIE increase,while the level of BDNF de-creases,indicating that they have certain value in the prognosis evaluation of neonates with HIE.