Background: Hemodialysis' adolescents facing unique and complex self-care activities. Enhancement of self-care activities of hemodialysis' adolescents is crucial for improving their ability to perform their daily living activities. Aim: Evaluate the effect of educational program regarding self-care health behavior on knowledge and practice of hemodialysis' adolescents. Design: A quasi-experimental design was used (one group pre and post). Setting: the study was conducted at hemodialysis unit in El-Tadamon hospital, El-Mabara hospital and El-Nasr Specialized hospital in Port Said City. Subjects: A convenience sampling of 55 hemodialysis' adolescents. Tools: Two tools were used to conduct this study; Tool (1) Structure interviewed questionnaire and Tool (2) Self Care Management Scale which consisted of two subscales: Sub scale (A): universal self-care factors and Sub scale (B): health-deviation self-care factors. Results: There were statistical significant relation between total knowledge scores of the studied adolescents and their total practices mean scores regarding universal self-care and health deviation self-care for health behavior. Conclusion: The educational program succeeded in improving the knowledge and practice of hemodialysis' adolescents regarding self-care health behavior on post and follow up tests than on pre-test. Recommendations: the study emphasized on the importance of ongoing in-service education programs regarding self-care health behavior to enhance the quality of life for hemodialysis pediatric patient.