Background: Neonatal hyperbilirubinemia is one of most common issues at neonatal stage, as a result, foot reflexology is one of the most popular forms of therapy and is useful for both preserving and treating health. Aimed of the present study was to determine the effect of foot reflexology on physiological index for neonates with hyperbilirubinemia at Neonatal Intensive Care Unit Design: A quasi-experimental research design was utilized. Setting: Neonatal Intensive Care Unit (NICU) at Assiut University Children Hospital. Subjects: A convenience sample included sixty neonates with hyperbilirubinemia. Tools: Two tools were utilized to gather the required data. (tool 1) structure questionnaire form, (tool 2) The physiological index evaluation form. Results: On the fifth day following the foot reflexology intervention, neonates in the study group's mean heart rate was 144.50±5.84 b/m, while those in the control group was 141.30±6.37 b/m. Neonates in the study and the control groups' mean respiratory rates were 46.20±5.52, 44.13±4.36 c/m respectively. Mean oxygen saturation was 94.13±1.35, and 91.93±0.82 for neonates in the study and the control groups respectively. Conclusion: Foot reflexology had an influential effect on stabilization and improving physiological index for neonates with hyperbilirubinemia. Recommendations: Foot reflexology is a safe, economical, and well-tolerated modality for neonates and it should be considered as an adjunctive modality that is integrated into nursing care.