This case-control study was therefore designed to examine the associations of ABO incompatibility, G6PD deficiency, and the polymorphisms of the UGT1A1, OATP1B1, and HO-1 genes with neonatal hyperbilirubinemia in Southeastern China, and the results of multivariate logistic regression analyses showed that the mutant genotype of rs4148323 in the UGT1A1 gene, ABO incompatibility, G6PD deficiency, and the SS genotype of the (GT)n repeats in the promoter region of the HO-1 gene were genetic risk factors for neonatal hyperbilirubinemia in Southeastern China. This evidence concerns the gene HMOX1 and G6PD deficiency.