Health related quality of life (HRQoL) is a major health issue for the junior high school students which should be emphasized. The main purposes of this study were to understand HRQoL among junior high school students and to explore its determinants. A total of 1394 subjects (male 701 and female 648) who were randomly selected from seventh, eighth, and ninth grade in fourteen junior schools in northern five Counties and Cities, Taiwan completed a self-administered questionnaire. In this study, objective, subjective, and global HRQoL were measured as dependent variables; social support was to be the mediated variable, personal, family, school, and internet use characteristics were to be independent variables to identify their relationships with global HRQoL. The main findings were as follow: (1) A significantly positive relationship was found between objective HRQoL (life conditions) and subjective HRQoL (life satisfaction). For HRQoL, including objective, subjective, as well as global HRQoL all revealed moderate high degrees. (2) Among four domains of HRQoL, the highest score was noted for ‘social domain’; whereas the lowest score was in ‘psychological domain’. (3) Gender comparison revealed that male revealed significantly good qualities in global HRQoL, as well as three domains (physical, psychological, and environmental domains); whereas female only revealed a significantly good quality in social domain HRQoL than male. (4) Multiple stepwise regression analyses on global HRQoL indicating eleven variables (perceived health status, family support, subject-father relationship, school support, family economic status, whether only child or not, gender, web-site friends, subject-mother relationship, mother’s education, and subject-classmate relationship) could be singled out as significant factors and accounted for 28. 4% of the variance. Perceived health status was the most important predictor which accounted for 15. 6% of the variance. Family support was the second important predictor and accounted for 7. 2% revealing a significantly higher importance than school support which only accounted for 0. 9% of the variance. (5) According to Structural Equation Model (SEM) analysis, a modified model was proposed with a good fit of the model. The main findings of SEM showed that social support (mainly for family and school support) not only directly influenced on HRQoL but was identified to be the mediated variable for independent variables including gender, whether only child or not, perceived health status, family economic status, subject-father relationship, subject-mother relationship, and subject-classmate relationship. These independent variables directly and indirectly affected HRQoL. Additionally, a significantly positive relationship was found between family support and school support. Based on our findings, we provide concrete direction for improving adolescents’ HRQoL. We also suggest building more strength social support, improving health status, and stressing parent-adolescent relationship would be helpful in improving HRQoL for junior high school students.