This study assessed the relationships between socioecononic status (SES), social support, oral health beliefs, psychosocial factors, health-related behaviours and health-related quality of life (HRQoL) in adolescents.A school-based follow-up study involving 376 12-year-old adolescents was conducted in Manaus, Brazil. Baseline data included sociodemographic characteristics (sex, parental schooling, family income, household overcrowding and number of goods), social support (SSA questionnaire), oral health beliefs and psychosocial factors (Sense of Coherence [SOC-13 scale] and self-esteem [Rosenberg Self-Esteem Scale]). Health-related behaviours (toothbrushing frequency, sedentary behaviour, smoking and sugar consumption) and HRQoL [KINDL questionnaire] were assessed at 6-month follow-up. Structural Equation Modelling assessed the relationships between variables.Greater social support (β = 0.30), higher SOC (β = 0.23), higher self-esteem (β = 0.23), higher toothbrushing frequency (β = 0.14) and less smoking (β = - 0.14) were directly linked with better HRQoL. SES (β = 0.05), social support (β = 0.26), oral health beliefs (β = - 0.02) were indirectly linked to HRQoL. Higher SES directly predicted higher toothbrushing frequency (β = 0.14) and less smoking (β = - 0.22). Greater social support also directly predicted higher SOC (β = 0.55), positive oral health beliefs (β = - 0.31) and higher self-esteem (β = 0.58). Greater social support indirectly predicted less smoking via oral health beliefs (β = - 0.05) and less sugar consumption via SOC (β = - 0.07).Socioeconomic status, social support, oral health beliefs and psychosocial factors were important predictors of adolescent's health behaviours and HRQoL over 6-month period through direct and indirect mechanisms. Health behaviours also directly influenced HRQoL.