Objective To investigate the correlation of serum levels of Krüppel-like transcription factor 2(KLF2)and angiopoietin-1(Ang1)with the severity and prognosis of neonatal respiratory distress syndrome(NRDS).Methods A total of 416 children with NRDS who were treated in this hospital from January 2019 to December 2022 were selected as the NRDS group.According to the results of chest imaging examination,the NRDS group was divided into mild group(145 cases),moderate group(174 cases)and severe group(97 ca-ses).According to NRDS outcome the children were divided into the good prognosis group 322 cases and bad prognosis group 94 cases,another 150 healthy premature infants were selected as the control group in the hos-pital.Serum KLF2,Ang1 levels were measured by enzyme-linked immunosorbent assay(ELISA).Pearson correlation was used to analyze the correlation between serum KLF2,Ang1 levels and neonatal acute physiolo-gy score perinatal supplement Ⅱ(SNAPPE-Ⅱ),1 min Apgar score in neonates with NRDS.The receiver op-erating characteristic(ROC)curve was used to evaluate the value of serum KLF2,Ang1 levels in predicting the prognosis of children with NRDS.Results Compared with the control group,the NRDS group had signifi-cantly lower birth weight and serum KLF2,Ang1 levels(P<0.05).In the children with NRDS,the serum of KLF2,Ang1 levels and 1 min Apgar score gradually decreased with the increase in the severity of the disease(P<0.05).Compared with the good prognosis group,the children with NRDS in the poor prognosis group had significant decreased in the serum KLF2 and Ang1 levels and a significant increased in the SNAPPE-Ⅱscore(P<0.05).In children with NRDS,the serum levels of KLF2 and Ang1 were negatively correlated with SNAPPE-Ⅱ score and positively correlated with 1 min Apgar score(P<0.05).The area under the curve(AUC)of serum KLF2 and Ang1 levels in predicting the poor prognosis of NRDS children were 0.931 and 0.909,respectively.The AUC of the combination of KLF2 and Ang1 in predicting the poor prognosis of NRDS children was 0.949,which was higher than that of KLF2 or Ang1 alone,with a sensitivity of 96.81%.Conclu-sion Serum KLF2,Ang1 levels in children with NRDS are reduced,the two level with NRDS children with severe degree aggravating gradually decreas,and both have important value in predicting the prognosis of chil-dren with NRDS.