Objective To explore the clinical significance of the serum brain?derived neurotrophic factor( BDNF) level in severe neonatal hyperbilirubinemia. Methods One hundred and twenty term and birth weight>2500 g infants admitted to the Neonatal Intensive Care Unit of Bethune nternational Peace Hospital of People Liberation Army were divided into severe hyperbilirubinemia group and control group according to their total bilirubin concentration. Total bilirubin( TBIL) concentration,BDNF and albumin in serum were determined in two groups. In addition, craniocerebral MRI was performed in severe neonatal hyperbilirubinemia before discharge. The correlation of the BDNF, TBIL, B/A, MRI results between severe hyperbilirubinemia group and control group were compared. Results The serum BDNF levels in severe hyperbilirubinemia group was ( 8. 84 ±3. 26) μg/L,significantly higher than that in control group((6. 24±1. 71) μg/L,t=3. 88,P<0. 05). In severe hyperbilirubinemia group,BDNF level was positively correlated with B/A level(r=0. 429,P<0. 05),but there was no correlation between BDNF and total bilirubin level(r=0. 278,P>0. 05). The serum BDNF level with craniocerebral MRI abnormal was ( 9. 53 ± 2. 77 ) μg/L, higher than that with craniocerebral MRI abnormal ((7. 81±3. 76) μg/L),but there was no statistical difference between them(t=1. 439,P>0. 05). Conclusion In severe neonatal hyperbilirubinemia, the body can secrete BDNF increasely. BDNF level is positivelycorrelated with B/ A level. As a marker of brain damage,BDNF is sensitive than craniocerebral MRI.