The WHOQOL-BREF is one of the cross-cultural and widely used measures for assessing health-related quality of life (HRQOL). Previous studies of the HRQOL using the WHOQOL-BREF mainly focused on adult; however, there has been less work carried out on assessing the HRQOL on early adolescence. The goal of this study was to examine the applicability of the WHOQOL-BREF Taiwan version in early adolescent sample. A total of 365 junior high school students participated in this study. Participants completed the WHOQOL-BREF Taiwan version and five visual-analogue items on HRQOL evaluation. The results supported the originally designed four-factor model, and also indicated good item discrimination, internal reliability, factorial validity (by using confirmatory factor analysis) and construct validity (e.g., predictive validity, discriminant and convergent validity) after deleting two physical health items (i.e., “To what extent do you feel that your pain hinders you in doing what you need to do”; “Do you need medical treatment to cope with your daily life?”) and one social relationships item (i.e., “Are you satisfied with your sex life?”). Overall, this study provides the applicability of the WHOQOL-BREF Taiwan version in early adolescence. In addition, the WHOQOL-BREF Taiwan version may be of use to health professionals in the assessment and comparison of different age groups from early adolescence to adulthood.