Background: Retinoblastoma is a malignant (cancerous) tumor that occurs in the retina of the eye. Mothers play an important role in caring for their children suffering from retinoblastoma. They must easily learn and follow treatment protocols, recognize and react to severe and distressing adverse effects of treatment. Aim of the study: The aim of the study was to evaluate the effect of health educational program for mothers regarding care of their children with retinoblastoma. Research design: A quasi-experimental design was utilized in this study. Setting: The study was conducted at Oncology Outpatient Clinics affiliated with Rod Al-Farag Hospital in Cairo City. Study subjects: A purposive sample of 45 mothers having children with retinoblastoma. Tools of data collection: Two tools were used in this study: Tool (I): An interviewing questionnaire including: a): Mothers demographic characteristics and personal characteristics of children, b): Medical history of children suffering from retinoblastoma, c): Mothers knowledge about retinoblastoma and d): Mothers practices to care of their children with retinoblastoma. Tool (II): Likert scale used to assess mothers' attitudes regarding to care of their children with retinoblastoma. Results: 4.4% of the studied mothers had good total knowledge level pre-program implementation which improved to 71.1% post-program implementation, 46.7% of the studied mothers had satisfactory total practices level pre-program implementation and then this percentage improved to 86.7% post -program implementation.  Also, 31.1 % of the studied mothers had positive total attitude level pre-program implementation which improved to 77.8 % post-program implementation. Conclusion: The health educational program achieved significant improvement in mothers' knowledge, practices and attitude. Recommendations: Providing continuous health educational program to mothers in Outpatient Clinics to improve their knowledge, practices and attitudes about retinoblastoma for their children.