Abstract : Background objectives: There are limited data on health-related quality of life (HRQOL) related to Indian children. The objective of this study was to construct a generic HRQOL reference for children aged 2-18 yr from a community setting. Methods: The study was a community-based cross-sectional survey. A total of 719 children/adolescents in the age group of 2-18 yr were enrolled using stratified random cluster sampling. A total of 40 clusters (cluster size 18) were selected for the study. The data contained child self-report and parent proxy report from healthy children and their parents/caretakers. The Pediatric Quality of Life Inventory 4.0 (PedsQL4.0) Generic Core Scale was used to collect HRQOL data. Questionnaires were self-administered for parents and children aged 8-18 yr. In the age group of five to seven years, parents assisted the children in filling questionnaires. Results: The mean HRQOL total scores from child self-report and parent proxy report were 87.50±11.10 and 90.10±9.50 respectively, for children aged 2-18 yr. Social functioning had the highest scores and emotional functioning had the lowest scores for the entire sample and subgroups. The mean values for HRQOL in the current study were significantly different from the reference study for both child (87.39 vs. 83.91, P0.001) and parent proxy reports (90.03 vs. 82.29, P0.001) when compared between children aged 2-16 yr. Interpretation conclusions: The study provided reference values for HRQOL in healthy children and adolescents from Kerala, India, that appeared to be different from existing international reference. Similar studies need to be done in different parts of India to generate a country-specific HRQOL reference for Indian children. © 2017, Indian Council of Medical Research. All rights reserved.