Background: Health of the adolescents is an important determinant of adult health. Multiple factors may affect the adolescents' health. Aim: This exploratory cross‑sectional study was to explore the effects of life stress, social support, and family hardiness on quality of life (QoL) in rural adolescents (15 to 19 years old) whose family had encountered adverse disaster events. Methods: Purposive sampling was used to recruit 350 adolescents met study criteria with 265 completing all questionnaires (response rate = 75.71%). Based on stress process model, we hypothesized that life stress and social support would directly and indirectly influence QoL, and family hardiness mediates the effects of life stress on QoL. Path analysis was employed to analyze the association among life stress, social support, family hardiness, and QoL. Results: The study showed that life stress, social support and family hardiness are significantly associated with adolescents' QoL: life stress (β = - 0.30, P < 0.001), social support (β = 0.18, P = 0.010), and family hardiness (β = 0.21, P = 0.002). Life stress and social support had significant association with family hardiness: life stress (β = -0.23, P = 0.001) and social support (β = 0.29, P < 0.001). Conclusion: Life stress directly and indirectly influences QoL through family hardiness. Family hardiness can buffer the effects of life stress. Social support could improve the adolescents' QoL. To promote QoL, it is important for healthcare providers to attend rural adolescents' life stress, and provide psychosocial interventions to enhance family hardiness and social support.