Background: Thalassemia is one of the most common human genetic disease which affects overall health of children. Approximately 20% of all children have a chronic illness like thalassemia and 65% suffer an illness severe enough to interfere with daily activities. It is very difficult for both the children and their parents to deal with thalassemia and its treatment. Children with thalassemia often experience poor quality of life due to regular blood transfusion, frequent visit to hospital etc. Successful family adaptation to chronic illness needs nursing interventions. Objectives: objectives of the study were to assess and compare the quality of life of children with thalassemia in experimental and control group; to determine the association of level of quality of life of children with thalassemia with selected variables. Methods: The quasi experimental study following pretest posttest research design was conducted among 107 parents and their thalassemic children (54 in experimental and 53 in control group) in selected hospitals in Delhi. Pretest and posttest quality of life of children with thalassemia (day 30 and day 60) were assessed using a valid and reliable PedsQL inventory. Results: Data was analyzed using SPSS 16; level of significance was kept at 0.05 level, the ‘t’ values computed between independent means of pretest quality of life scores in experimental and control group were not significant at 0.05 level. It indicated that subjects in experimental group and control group did not differ significantly in terms of quality of life scores of children regarding care of children with thalassemia. In experimental group, a statistical significant difference was found between the mean pretest and posttest quality of life scores of children with thalassemia (5-12 yrs) on day 30 and day 60 (p<.05). The mean posttest quality of life scores of children with thalassemia (8-12 years) in experimental and control group on day 60 was statistically significant and it was not found significant on day 30 (p< 0.05). A significant association was observed between age of initiation of treatment and quality of life of children (p=0.03); hemoglobin level and quality of life of children with thalassemia (p=0.0). Discussion: In the current study, a significant increase in quality of life of children was observed after administration of STP on care of children with thalassemia for parents. Similar significant changes have been reported by Kargar Najafi et al. Study also highlights that nursing intervention can help parents to better understand and identify coping strategies which will allow them to gain control over their children’s illness and their family life. So it is recommended to assess the knowledge of the staff nurses working in thalassemia unit to educate the parents and improve the quality of life of children with thalassemia.