Abstract: Objective To study the causes of severe hyperbilirubinemia and the therapeutic effect of neonatal severe hyperbilirubinemia in Sanshui District.Methods A total of 751 cases of severe hyperbilirubinemia admitted to our hospital from January 2016 to December-2016 were selected as the research subjects. The causes of the disease were analyzed. The targeted treatment was applied and the therapeutic effect was observed.Results After observing all the neonatal morbidity reason and treatment effect, that the main causes of severe hyperbilirubinemia were infection, premature delivery and G6 PD. After treatment, the neonatal total bilirubin, indirect bilirubin, platelet (PLT), white blood cell (WBC) and hemoglobin (Hb) levels were significantly improved compared with before treatment. The difference was statistically significant (t=214.102, 197.036, -14.316, 33.491, 31.030, P<0.05).Conclusions Neonatal severe hyperbilirubinemia is mainly caused by infection, premature delivery and G6 PD. Timely effective treatment can significantly improve bilirubin level and hematological indexes, promote recovery and provide effective protection for prognosis.