Dissertation (MSc Paediatric Nursing)Background: Children with sickle cell disease are prone to a multitude of disease related complications, improving caregivers' knowledge on common precipitate factors of sickle related complication and encouraging home based preventive intervention can change the overall wellbeing of these children. This study aimed to evaluate the level of knowledge and based practice of caregivers and its relation to SCD control. Methods: Quantitative hospital based cross-sectional analytical study. Convenient sampling procedure was used to enroll children with SCD and their caregivers. Semi structured questionnaire interviewer administered, were used for data collection. Data entry, processing and analysis were done by using (SPSS v. 21). Results: A total of 300 caregivers and their SCD children were enrolled. Out of these enrolled subjects, 53.3% had inadequate knowledge and 52% of the caregivers, had inappropriate home- based practice for prevention SCD complications. Out of the children enrolled 89% had at least one complication for the past 6 months. Both caregivers knowledge (AOR 2.282, 95% CI [1.021, 5.103] p=0.044) and home-based practice (AOR 3.030, 95% CI [1.338, 6.862] p=0.008), were significantly associated with high occurrence of sickle cell disease complications. The under 5 children with SCD also had 2 times higher risk of developing SCD related complications (AOR 2.760, 95%CI [1.192, 6.391] p value 0.018). Conclusions: The study has shown that a significant proportion of caretakers of children with SCD had a low knowledge about sickle cell disease and its complications, which was also reflected by poor adherence to the recommended home-based intervention. Key word: Sickle cell disease, Knowledge, home-based practice and frequency of SCD complications.