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Purpose: Nasopharyngeal carcinoma (NPC) is one of the most malignant head and neck carcinomas with unique epidemiological features. In this study, we aimed to identify the novel NPC-related genes and biological pathways, shedding light on the potential molecular mechanisms of NPC. Methods: Based on Gene Expression Omnibus (GEO) database, an integrated analysis of microarrays studies was performed to identify differentially expressed genes (DEGs) and differentially methylated genes (DMGs) in NPC compared to normal control. The genes which were both differentially expressed and differentially methylated were identified. Functional annotation and protein–protein interaction (PPI) network construction were used to uncover biological functions of DEGs. Results: Two DNA methylation and five gene expression datasets were incorporated. A total of 1074 genes were up-regulated and 939 genes were down-regulated in NPC were identified. A total of 719 differential methylation CpG sites (DMCs) including 1 hypermethylated sites and 718 hypomethylated sites were identified. Among which, 11 genes were both DEGs and DMGs in NPC. Pathways in cancer, p53 signaling pathway and Epstein–Barr virus infection were three pathways significantly enriched pathways in DEmRNAs of NPC. The PPI network of top 50 DEGs were consisted of 191 nodes and 191 edges. Conclusions: Our study was helpful to elucidate the underlying mechanism of NPC and provide clues for therapeutic methods. [ABSTRACT FROM AUTHOR]