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The aim of this prognostic factor analysis was to investigate if a patient's self-reported health-related quality of life (HRQOL) provided independent prognostic information for survival in non-small cell lung cancer (NSCLC) patients.Pretreatment HRQOL was measured in 391 advanced NSCLC patients using the EORTC QLQ-C30 and the EORTC Lung Cancer module (QLQ-LC13). The Cox proportional hazards regression model was used for both univariate and multivariate analyses of survival. In addition, a bootstrap validation technique was used to assess the stability of the outcomes.The final multivariate Cox regression model retained four parameters as independent prognostic factors for survival: male gender with a hazard ratio (HR)=1.32 (95% CI 1.03–1.69; P=0.03); performance status (0 to 1 versus 2) with HR=1.63 (95% CI 1.04–2.54; P=0.032); patient's self-reported score of pain with HR=1.11 (95% CI 1.07–1.16; P < 0.001) and dysphagia with HR=1.12 (95% CI 1.04–1.21; P=0.003). A 10-point shift worse in the scale measuring pain and dysphagia translated into an 11% and 12% increased in the likelihood of death respectively. A risk group categorization was also developed.The results suggest that patients' self-reported HRQOL provide independent prognostic information for survival. This finding supports the collection of such data in routine clinical practice.