BackgroundUnderstanding how health-related quality of life (HRQoL) is related to lifestyle factors during adolescence is crucial to effective health promotion. The aim of this analysis was to identify associations between HRQoL and lifestyle and to determine the degree to which they are mediated by food choices in adolescents.MethodsThe Wellbeing in Schools (NI) survey (N = 1609; 13–14 years) assessed HRQoL using the Kidscreen52. Food choice was assessed by Food Frequency Questionnaire (FFQ) and physical activity was assessed using the Physical Activity Questionnaire for Adolescents (PAQ-A). Social media and alcohol abstinence were self-reported.ResultsPath analysis indicated that fruit and vegetable intake was associated with higher HRQoL on dimensions of moods and emotions, parent relations and home life, financial resources, and social support and peers. Bread and diary intake was related to higher physical wellbeing. Protein was associated with higher psychological wellbeing, moods and emotions, self-perception, parent relations and home life, financial resources, and lower social support and peers. Junk food was related to lower moods and emotions. Males had higher psychological wellbeing, moods and emotions, parental relations and home life. Females had higher self-perception, autonomy, and social support and peers. Greater physical activity explained higher HRQoL on all dimensions. Less social media was associated with higher psychological wellbeing, moods and emotions, self-perception, parent relations and home life, and school environment. Alcohol abstinence was associated with higher physical wellbeing, psychological wellbeing, moods and emotions, self-perception, parent relations and home life, and school environment dimensions.ConclusionIntervention to promote HRQoL in adolescents should consider food choices whilst encouraging physical activity, discouraging social media and deterring alcohol, and targeting boys and girls separately.