Studies that have investigated the health-related quality of life (HRQoL) of adolescents facing a parental illness showed inconsistent results, and none used a person-oriented approach allowing for a deeper understanding of their experience. The aim of this study was to compare the HRQoL of adolescents facing a parental illness to that of their peers, and to explore their HRQoL through a person-oriented approach. The sample consisted of 1324 adolescents recruited in secondary schools (11-15 years old). Adolescents completed questionnaires assessing sociodemographic characteristics, parental illness, HRQoL (KIDSCREEN-52), and academic performance and caring activities (MACA-YC18). Adolescents facing a parental illness showed significantly lower HRQoL than their peers on all dimensions. The cluster analysis yielded five patterns of HRQoL among adolescents facing a parental illness: Low HRQoL; High HRQoL; Moderate HRQoL with High Social Acceptance; High Well-Being, High Moods and Emotions, and High Social Support and Peers. These clusters differed according to demographics, the type of parental illness, illness perception, academic performance, and level of caring activities. The Low HRQoL cluster showed especially low academic performance and high level of caring activities. This multidimensional HRQoL evaluation thus helps to foreground the diversity of these adolescents' experiences in order to better address their needs.