Purpose: Sickle cell disease (SCD) is a genetic blood disorder that increases the risk for recurrent painful episodes. Parents' knowledge regarding SCD management is poor, leading to poor symptom management and lower Health Related Quality of Life (HRQOL) in children with SCD. The purpose of this study was to examine the effects of a parent educational intervention program (PEIP) on the parental knowledge, self-efficacy and perception of the HRQOL of their children with SCD. Theoretical Framework: The HRQOL theoretical framework as proposed by Wilson and Clearly (1995) was used to guide the study. Social-Cognitive Learning Theory (Bandura, 1986) was used to explain the relationship between knowledge, self-efficacy and perceived HRQOL. Methods: Two groups of Omani parents of children with SCD were randomly assigned to either an experimental group (n = 37) receiving PEIP accessed on a smartphone + weekly phone reinforcement for four weeks, or a control group (n = 35) receiving Standard Educational Program (SEP) as part of standard of care. Outcome measures (Knowledge Questionnaire, Self-Efficacy Scale, and HRQOL-SCD + HRQOL-GENERIC were administered twice (at enrollment, and 4 weeks after enrollment). Statistical Package for Social Science, version 24 was used for data analyses. Results: Parents' knowledge and self-efficacy scores were significantly higher for the intervention group (PEIP) when compared to the SEP 4 weeks post intervention. Also, The total HRQOL scores were higher at 4 weeks compared to baseline, and were also higher in the PEIP compared to the SEP. Parents' knowledge, self-efficacy, use of hydroxyurea, child's age and gender, were significant predictors of HRQOL in children with SCD. Conclusion: PEIP delivered by using a smartphone was effective in improving the parents' knowledge, self-efficacy in symptom management, and parent and child perception of HRQOL. PEIP was innovative in that it targeted all dimensions of HRQOL in children with SCD. Finally, the family played an important role in the process of care and therefore, developing family-based interventions is the key factor for improving HRQOL in children with SCD. Implications: The study highlighted the effectiveness of smart phone technology for delivering a high quality educational intervention program for parents and their families. [The dissertation citations contained here are published with the permission of ProQuest LLC. Further reproduction is prohibited without permission. Copies of dissertations may be obtained by Telephone (800) 1-800-521-0600. Web page: http://www.proquest.com/en-US/products/dissertations/individuals.shtml.]