Objective: To investigate the predictive value of of serum NSE, umbilical cord blood albumin levels in hyperbilirubinemia full-term neonates with brain injury. Methods: 300 cases of hyperbilirubinemia full-term neonates in our hospital during January 2018 to November 2019 were chosen as hyperbilirubinemia group, 200 cases of healthy full-term neonates who were delivered in our hospital during the same period and whose general information matched were chosen as normal control group. According to whether the hyperbilirubinemia group had brain injury, they were further divided into bilirubin encephalopathy group(n=34) and non-bilirubin encephalopathy group(n=266). NSE, umbilical cord blood albumin levels in hyperbilirubinemia group and normal control group were compared. Clinical data, NSE and umbilical cord blood albumin levels between bilirubin encephalopathy group, non-bilirubin encephalopathy group were compared. Risk factors associated with brain injury in full-term newborn with hyperbilirubinemia were analyzed by logistics regression, predictive value of NSE and umbilical cord blood albumin on brain injury in full-term newborn with hyperbilirubinemia were evaluated by ROC curve. Results: NSE level in hyperbilirubinemia group was higher than that in normal control group(P0.05). Incidence of jaundice, anemia, indirect bilirubin peak, total bilirubin peak and NSE level in bilirubin encephalopathy group were higher than those in non-bilirubin encephalopathy group, level of umbilical cord blood albumin was lower than that in non-bilirubin encephalopathy group(P<0.05). Logistic regression analysis showed that jaundice, anemia, indirect bilirubin peak, total bilirubin peak, NSE and umbilical cord blood albumin within 24h after birth were risk factors for hyperbilirubinemia with brain injury(P<0.05). When NSE was 67.09 ng/mL, the yoden index was the highest, with sensitivity and specificity of 79.70％, 55.88％ respectively. When the umbilical cord blood albumin was 4.20mg/mL, the jorden index was the highest, sensitivity and specificity were 76.32％, 82.35％ respectively. Conclusion: Abnormal changes in serum NSE, umbilical cord blood albumin levels are observed in full-term neonates with hyperbilirubinemia, moreover they have value of early prediction for subsequent brain injury.