Thalassemia is one of the most common genetic blood disorders in the Mediterranean region. Few studies have investigated the beliefs regarding thalassemia, especially in a developing country. Aim: the study aimed to assess mothers’ performance regarding care of their children with thalassemia. Design: A descriptive research design was used in this study. Sample: Convenient sample included 286 mothers was used. Setting: Abo El-Rish Hematology Outpatient Clinics - Egypt. Tool: Interview questionnaire consisted of five parts. Part I: Demographic characteristics of mothers and their child, Part II: Medical history of children, Part III: Mothers’ knowledge regarding thalassemia, Part IV: Assess mothers’ attitudes. Part V: Assess mothers’ reported practices. Results: 40.20% of the studied mothers had poor total knowledge regarding thalassemia. 97.2% of the studied mothers had positive total attitude. 95.5% of the studied mothers had adequate total reported practices. There was a highly statistically significant relation between mothers’ knowledge and all items of demographic characteristics except residence item. Conclusion: Two fifths of studied mothers had poor knowledge, majority of them had positive attitude, and adequate total reported practices regarding thalassemia. There was highly statically significant positive correlation between total knowledge, reported practice, and not with attitude. Recommendation: Performing educational program to mothers who having children with thalassemia on a large scale.