Background: Sickle Cell Anemia (SCA) is a chronic hematologic disease associated with many physical, psychological, and social problems that can affect on quality of life. Self-learning guidelines has a great effect in improving quality of life and health status of adolescent with Sickle Cell Anemia. Aim of the study was to evaluate the effect of self-learning guidelines on quality of life and self-reported practice of adolescents with sickle cell anemia. Design: A quasi-experimental study. Settings: Inpatient and outpatient of pediatric hematology departments at Benha University and Benha Specialized Pediatric Hospitals. Study subjects: A purposive sample of 50 adolescents diagnosed with sickle cell anemia in the previously mentioned settings was included in the study throughout a period of six months. Data collection tools: A Structured interviewing questionnaire sheet, self-care reported practicesand pediatric quality of life scale. Results: There was a statistical significant difference between total knowledge and total self-reported practices of the studied adolescents regarding to sickle cell anemia post and follow up self-learning guidelines as compared to pre self-learning guidelines implementation. There was a statistical significant difference between the total score of quality of life for the studied adolescents regarding to sickle cell anemia at post and follow up compared to pre self-learning guidelines implementation. Conclusion: Self-learning guidelines implementation was effective in improving the quality of life of adolescents with sickle cell anemia through improving their knowledge and self-care reported practices. Recommendations: In service training program for adolescents with the sickle cell anemia to enhance their quality of life.Conducting premarital screening programs for raising awareness of children and adolescents regarding the nature hereditary of SCA& associated complication.