Objective To construct and verify a predictive model based on bilirubin levels in umbilical cord blood and clinical risk factors to predict the risk of hyperbilirubinemia in ABO neonatal hemolysis disease. Methods A total of 500 ABO-HDN children were selected as the modeling set. 100 ABO-HDN children served as the verification set. Depending on whether neonatal hyperbilirubin was occurring， they were divided into hyperbilirubinemia group and non-hyperbilirubin group（Non-HB）. The bilirubin level in umbilical cord blood was detected and the general and clinical data of children and mothers were collected. Multivariate Logistic regression analysis and ROC curve were used to evaluate the prediction efficiency of the prediction model of bilirubin levels in umbilical cord blood combined with clinical risk factors for the risk of NHB in ABO-HDN. Results There were 225 cases of NHB of the 500 ABO-HND children in the modeling set with an incidence of 45%. Unifactorial analysis showed that influencing factors were maternal age， premature rupture of membranes， pregnancy with hypertension， diabetes， thyroid disease and anemia， intrauterine distress， cranial hematoma， infection， gestational age， neonatal asphyxia， feeding patterns， low birth weight， intracranial hemorrhage， and respiratory distress（P < 0.05）. Multivariate Logistic regression analysis showed that the independent risk factors were premature birth， neonatal asphyxia， infection， G-6-PD deficiency，intracranial hemorrhage and respiratory distress（OR = 2.377， 7.457， 54.438， 45.487， 2.788，5.407， all P < 0.05）. Three models of bilirubin levels in umbilical cord blood，clinical risk factors and bilirubin levels in umbilical cord blood combined with clinical risk factors predicted the occurrence risk of NHB in ABO-HDN. And the area AUC values under ROC curve were 0.817（95%CI： 0.776 ~ 0.859）， 0.876（95%CI： 0.845 ~ 0.907） and 0.944（95%CI： 0.921 ~ 0.966）， respectively， all P < 0.05. The prediction model of bilirubin levels in umbilical cord blood combined with clinical risk factors was used to verify the practical efficacy of 100 ABO-HDN children in the verification set. The area AUC value under ROC curve was 0.951（95%CI： 0.776 ~ 0.859），P < 0.05. Conclusion The prediction model of bilirubin levels in umbilical cord blood combined with clinical risk factors can ccurately predicted the occurrence risk of NHB in ABO-HDN. It could provide objective reference for prevention， diagnosis， treatment and standardized management of NHB in ABO-HDN.