Objective To explore the main influence factors of neonatal hyperbilirubinemia (NHB), and to provide the clinical basis for the control and prevention of NHB. Methods A total of 147 NHB patients hospitalized in Danyang People's Hospital from October 2010 to October 2011 was selected as case group, 122 normal infants delivered in same hospital at the same period were recruited as control group.The serum bilirubin levels of infants were measured and the questionnaires to their parents were used for data collection.Multifactor logistic regression analysis was conducted to screening the mainly factors of the NHB. Results There were no significant differences in sex ratio, general data of patients and the control group in age (P>0.05).9 factors, including low birth weight, cesarean section, the lack of breast milk, meconium aspiration syndrome, elderly primipara, pregnancy-induced hypertension, infection, asphyxia, intrauterine distress were the main influencing factors of NHB. Conclusion It is necessary to strengthen the monitoring of elderly primipara, splits the palace production, meconium aspiration syndrome and infection in children with these perinatal risk factors, actively feeding and timely monitoring and intervention of serum bilirubin level, achieve the purpose of prevention and control of NHB.