Background: Hyperbilirubinemia is the most common problem in the newborn period that requiring hospitalization and medical attention. Approximately 60% of all newborns develop some degree of jaundice in the first week of life. Aim of the study: To assess mothers' knowledge and attitude regarding neonatal hyperbilirubinemia. Research design: A descriptive exploratory research design was used to achieve the aim of this study. Sample: A convenient sample of 375 mothers admitted to postpartum unit at Minia University Hospital for Obstetrics and Pediatrics. Tool: Structured interview questionnaire were developed by the researchers that include Part I: Personal data of the mothers including age, place of residence, level of education, occupation …etc. Part II: assessment of mothers' knowledge regarding neonatal hyperbilirubinemia. Part III: assessment of mothers' attitude regarding hyperbilirubinemia by using five levels Likert scale. Results: the results of the current study revealed that more than half of mothers had unsatisfactory level of knowledge regarding hyperbilirubinemia and the vast majority of them had an agree attitude toward hyperbilirubinemia. There was a fair a correlation between occupation and educational level of mothers and their total knowledge scores. More than half of mothers with past history of babies with hyperbilirubinemia have a satisfactory knowledge and there was no statistically a significance difference between mothers who have previous experience with hyperbilirubinemia and their attitudes to hyperbilirubinemia. Conclusion: More than half of mothers have an unsatisfactory knowledge regarding hyperbilirubinemia and the most of mothers have an agree attitude regarding hyperbilirubinemia. Recommendation: further health education program should be conducted to increase awareness of mother to how to deal and manage their newborn with hyperbilirubinemia.