Purpose: The purpose of this study is to identify novel molecular markers and potential molecular targets for NPC based on bioinformatics analysis.Methods: We used bioinformatics to analyze one miRNA and two mRNA expression microarray datasets from the Gene Expression Omnibus database. The study included nasopharyngeal tissue samples from 57 patients with NPC and 32 patients without NPC. Fifty-one screened differentially expressed genes (DEGs) were evaluated by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) signal pathway enrichment analyses, and a protein-protein interaction (PPI) network was constructed. Results: The GO analysis results showed that the DEGs were mainly related to cell cycle checkpoints, cell division, and DNA synthesis during DNA repair. The KEGG analysis results suggested that the DEGs were mainly associated with extracellular matrix receptor interactions. In the PPI network, we identified RAD51AP1, MAD2L1, SPP1, CCNE2, CNTNAP2, and MELK as hub genes, clustered a key module, and identified eight key transcription factors: TFII-I, Pax-5, STAT4, GR-alpha, YY1, C/EBPβ, GRβ, and TFIID. Conclusion: The hub genes and signaling pathways identified above may play an important role in NPC development and provide ideas for the selection of valuable prognostic markers and the development of new molecular-targeted drugs.