Lung cancer patients generally experience high levels of physical and psychological distress and decreased quality of life (QOL). Sense of coherence (SOC) has been conceptualized as a personality orientation reflecting the degree to which an individual perceives their world as comprehensible, manageable and meaningful. The present study investigated the associations of SOC with QOL in lung cancer. It also examined potential psychological mediators by which SOC may exert its influences on QOL. Fifty-six participants with non-small cell lung cancer were administered self-report assessments of SOC, QOL and psychological distress. Results revealed that SOC was positively associated with QOL and this relationship may be mediated by depressive symptoms. The current study supports the notion that SOC may be a protective factor with regard to psychological adjustment and QOL in cancer survivors.