The identification of cancer-related fatigue as a clinical problem in pediatric oncology is an important phenomenon, and there are limited number of studies about raising the awareness of pediatric oncology patients and their parents. Fatigue-related education for patients and their parents before and during cancer treatment reduces the fatigue levels of patients. This study aims to analyze the effect of fatigue-related education for pediatric oncology patients aged 7-12 and their parents on their fatigue and quality of life. This study was conducted with 80 children with cancer and their parents who were assigned to either the control group (n = 40) or the experimental group (n = 40). The experimental group received a fatigue-related educational program. The data were collected three times: prior to the program, 3 months later, and 6 months afterwards. Multidimensional variance analysis, the Bonferroni adjusted t test and regression analysis were used to analyze the data. A significant difference was found among the experimental and the control group for total mean scores and the mean scores of subdimensions of the Scale for the Assessment of Fatigue-Child Form in terms of the interactions of group, time, and group*time (p < 0.05). Significant differences were found among the experimental and control groups' mean scores on the Scale for the Quality of Life-Child and Parents Form in terms of the interactions of group, time, and group*time (p < 0.05). Fatigue-related education is an effective education model as a way to reduce fatigue and increase the quality of life of children with cancer. The use of fatigue-related education by nurses in pediatric oncology clinics will have positive effects on children and their parents.