Purpose: The purpose of this study was to assess the prognostic significance of pretreatment quality of life (QoL) scores and symptom scores in a group of patients treated with high dose radiotherapy. Material and methods: A total of 198 patients treated with external irradiation ( greater than or equal to 60 Gy) were included. In all these patients, baseline QoL was assessed using the EORTC QLQ-C30. The prognostic significance of a number of non-QoL and QoL parameters with regard to survival was estimated in both univariate and multivariate analyses. Results: In a multivariate model including the non-QoL parameters, performance status, weight loss and N-classification were independent prognostic factors for survival. After entering the QoL parameters in the model, global QoL was the strongest prognostic factor, while performance status lost its significance. Subsequently, a significant interaction term was found between N-classification and global QoL, indicating that global QoL was an independent prognostic factor but that the effect varied as a function of N-status. In N+ patients, the median survival in the group with low scores for global QoL was 4.5 months, which was significantly worse (P <0.0001) compared with the high score group in which the median survival was 12.9 months. Conclusion: Global QoL is a strong prognostic factor for survival in patients with NSCLC who have pathological lymph nodes at presentation and who are treated with radical or curative radiotherapy.