ABSTRACT: Nasopharyngeal carcinoma (NPC) is one of the most common malignancies in the head and neck. The aim of the current study was to identify the key pathways and genes involved in NPC through bioinformatics analysis and to identify potential molecular mechanisms underlying NPC proliferation and progression. Three gene expression profiles (GSE12452, GSE34573 and GSE64634) were downloaded from the Gene Expression Omnibus database. A total of 76 samples were analyzed, of which 59 were NPC samples and 17 were normal samples. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were subsequently conducted. The protein-protein interaction (PPI) network of the differentially expressed genes (DEGs) was constructed using Cytoscape software. Analysis of GSE12452, GSE34573 and GSE64634 datasets identified 1,301 (553 upregulated and 748 downregulated), 1,232 (348 upregulated and 884 downregulated) and 1,218 (555 upregulated and 663 downregulated) DEGs, respectively. Using Venn diagram analysis, 268 DEGs (59 upregulated and 209 downregulated) that intersected all three datasets, were selected for further analysis. The results of GO analysis revealed that upregulated DEGs were significantly enriched in biological processes, including 'cell adhesion', 'cell division', 'mitosis' and 'mitotic cell cycle'. The downregulated DEGs were mainly enriched in 'microtubule-based movement', 'cilium movement', 'cilium axoneme assembly' and 'epithelial cell differentiation'. The KEGG pathway analysis results revealed that the upregulated DEGs were highly associated with several pathways, including 'extracellular matrix-receptor interaction', 'human papillomavirus infection', 'arrhythmogenic right ventricular cardiomyopathy' and 'focal adhesion', whereas the downregulated DEGs were enriched in 'metabolic pathways', 'Huntington's disease', 'fluid shear stress and atherosclerosis' and 'chemical carcinogenesis'. On the basis of the PPI network of the DEGs, the following top 10 hub genes were identified: Dynein axonemal light intermediate chain 1, dynein axonemal intermediate chain 2, calmodulin 1, coiled-coil domain containing 114, dynein axonemal heavy chain 5, radial spoke head 9 homolog, radial spoke head component 4A, NDC80 kinetochore complex component, thymidylate synthetase and coiled-coil domain containing 39. In conclusion, by performing a comprehensive bioinformatics analysis of DEGs, putative targets that could be used to elucidate the molecular mechanisms underlying NPC were identified.