Objective To investigate the effects of exchange transfusion therapy on biochemical indexes and blood internal environment in neonates with jaundice. Methods From Jan. 2010 to Dec.2016, a total of 58 neonates with jaundice treated in neonatal intensive care unit (NICU) of our hospital for exchange transfusion therapy were selected as the clinical objects. The changes of serum bilirubin level, biochemical indexes (blood calcium, blood sodium, blood potassium, blood sugar) and blood routine indexes [white blood cell count (WBC), red blood cell count (RBC), hemoglobin (HGB), hematocrit (HCT), platelet (PLT)] were compared before and after exchange transfusion therapy in 58 neonates with jaundice. Results After exchange transfusion therapy, there was no significant changes in the levels of serum calcium, blood sodium, RBC, HGB and HCT compared with those before therapy (P>0.05), and the levels of total bilirubin, indirect bilirubin, direct bilirubin, blood potassium, WBC and PLT were significantly lower than those before therapy while the level of blood sugar was significantly higher than that before therapy (P<0.05). Conclusion Exchange transfusion therapy whose effect on blood biochemical indexes and blood internal environment is great, can not only effectively reduce the serum bilirubin level of neonates with jaundice, but also improve the clinical symptoms of neonatal jaundice. Therefore, the indications of blood exchange should be strictly controlled, and the biochemical indexes and blood routine indexes of children should be monitored after operation