Neonatal hemolytic disease refers to the production of blood group antibodies in the mother’s body that do not match the fetal blood group antigens due to a mother-child blood group mismatch, and this antibody enters the fetus through the placenta causing homozygous immune hemolysis, commonly in the Rh blood group system and ABO blood group system. Other causes of hemolysis in the neonatal period are defects in red blood cell enzymes or red blood cell membranes, all of which have proprietary names, and only hemolysis of mismatched blood groups is called neonatal hemolytic disease. Rh blood group incompatibility and ABO blood group incompatibility between mother and fetus are the main causes of neonatal hemolytic disease. The blood type of the fetus is determined by both parents. If the fetus inherits blood group antigens from the father that the mother does not have, the fetal red blood cells enter the mother’s body and cause the mother to produce the corresponding antibodies, which then enter the fetus through the placenta, resulting in an immune reaction of antigenic antibodies and hemolysis, which is more common when the mother has O blood type and the child has A, B or AB blood type, or when the mother has Rh negative blood and the child has Rh positive blood. The clinical manifestations include jaundice and anemia. Jaundice appears early, is severe and progresses rapidly, and bilirubin encephalopathy may occur without timely intervention. Diagnosis is divided into prenatal and postnatal diagnosis. Treatment includes phototherapy, medication (intravenous gammaglobulin, albumin), blood exchange and correction of anemia.