The aim of the present study was to evaluate validity and reliability of the Health Related Quality of Life Index KIDSCREEN-10 in a sample of Iranian school students. Using multistage sampling, 551 middle and high school students were selected in Yazd and answered to KIDSCREEN-10 index. Each 100 students also completed one more questionnaire (included in research tools). To verify the reliability of the questionnaire, Cronbach’s alpha measure and test-retest reliability (intraclass correlation coefficient) were used and Confirmatory factor analysis and correlation analysis methods were employed to assess the construct validity and convergent validity of the questionnaire. Cronbach’s alpha (0.80) and intraclass correlation coefficient (0.85) confirmed reliability of the questionnaire, and Confirmatory Factor Analysis indicated a unidimentional structure for the questionnaire. Moreover, obtained a high correlation between the total score of the KIDSCREEN-10 index and the total scores obtained from other indices was an indicative of convergent validity for the scale. However, the correlations obtained for the KIDSCREEN-10 index with the dimensions in the other questionnaires varied from low (for Multidimensional Students’ Life Satisfaction Scales) to moderate and high (for KIDSCREEN-52, Pediatric Quality of Life Inventory, General Health Questionnaire-28, Personal Well-Being Index—School Children, and Coopersmith Self Esteem Inventory). Significant differences in quality of life scores were found between male and female students of 11 to 15 and 16 to 19 year old, whereas such a difference was absent in psychological and socio-economic status. Overall, the KIDSCREEN-10 has an acceptable validity and reliability in Iranian students and can be used for health care polices and research projects here in this country.