Background: Phototherapy is the main therapeutic interference for neonatal hyperbilirubinemia used to escape an exchange transfusion and to decrease the risk of bilirubin-induced encephalopathy (kernikterus). Phototherapy has an oxidative effect on cell components and cell membranes by enhancing peroxidation of lipid and damage to DNA. Many genes function as apoptosis regulatory genes. Examples of these genes involve the BCL2 gene as an anti-apoptotic oncogene, and the BAX gene which is a promoter of apoptosis. We aimed to evaluate the effect of phototherapy on expression of BAX and Bcl2 genes in hyperbilirubinemic fullterm neonates. Eighteen full-term neonates with indirect hyperbilirubinemia who received phototherapy for 24 h were enrolled as a study group and nine apparently healthy full-term neonates with a normal serum bilirubin level were included as a control group. Assessment of the anti-apoptotic effect(s) of BCL2 and the pro-apoptotic effect(s) of (Bax) genes was achieved by quantitative assay of their products (BCL2 and BAX proteins) by ELISA assay after phototherapy. Results: Significant decrease in the bcl2 (p < 0.001) and increase in Bax protein (p < 0.001) serum levels after phototherapy in hyperbilirubinemic full-term neonates. Conclusion: Hyperbilirubinemia has no apoptotic influence, while phototherapy induces apoptosis in the peripheral blood of hyperbilirubinemic full-term infants.