Background Epstein-Barr virus (EBV) infection is one of the most important factors of nasopharyngeal carcinoma (NPC)endemic areas.Transcription of EBV-encoded non-polyadenylated RNAs (EBERs) are presented in most of NPC tumors.Exploring EBERs as a prognostic marker for NPC might further be informative about the biology and the progression of the disease.The aim of this study was to analyze the role of EBV latency in the clinical management of nasopharyngeal carcinoma (NPC),by detecting EBERs.Methods RNA in situ hybridization (ISH) for detecting EBERs was carried out on 908 NPC tumor tissues.Overall survival (OS) curves were analyzed with the Kaplan-Meier method and the Cox proportional-hazards regression models.Results The median follow-up time was 70 months (1-120 months).Eight hundred and sixteen (89.9％) from a total of 908 consecutive NPC cases were found to be EBV-EBER positive.EBER-ISH staining revealed nuclear localization in NPC cells.In the Kaplan-Meier analysis for OS,high EBER expression levels in NPC patients were statistically significant positive prognostic factors for survival (log-rank,P=0.022),especially in adults aged 17-40 years (P=0.023) and in those with advanced stage disease (log-rank,P=0.002).Cox proportional-hazards regression model analysis showed that the EBER expression level was an independent risk factor for OS (hazard ratio 0.724,P=0.005).Conclusions EBERs were frequently detected in NPC tumor tissues,and high-level EBER expression correlated with good prognosis in NPC patients,especially in adult patients and in those with advanced stage disease.EBER may serve as a potential prognostic predictor in NPC.