Objective To analyze the effect of quality of life (QOL) on the prognosis of long-term survivors with nasopharyngeal carcinoma (NPC). Methods A total of 192 NPC patients treated between 1999 and 2000 and with tumor-free survival before July 2003 were enrolled in this study. All patients received QOL measurement between July and August in 2003. Measurement scales included Chinese SF-36 questionnaire and a checklist consisting of fourteen items about self-rating symptoms. The median follow-up time was 7.9S years (range 2.67-9.55 years). The effects of QOL, social demographic and clinical factors on prognosis were analyzed. Results Univariate analysis showed that QOL affected the tumor-free survival and overall survival. Multivariate analysis showed that hypomnesia was an independent prognostic factor of tumor-free survival, while trismus, headache and age were independent prognostic factors of overall survival. The younger and the better QOL had better prognosis. The other sociodemographic and clinical factors had no prognostic value. Conclusion QOL is an important factor affecting the prognosis of long-term survivors with NPC, and it should be routinely evaluated during the follow-up.