The purpose of this study was to investigate novel biomarkers and potential mechanisms in nasopharyngeal carcinoma (NPC) patients with metastasis.Two microarray datasets (GSE103611 and GSE36682) were obtained from GEO database, differentially expressed genes (DEGs) and differentially expressed miRNA (DEMs) were identified, Gene ontology (GO) as well as Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were conducted with DEGs and DEMs targeted genes. Protein-protein interactions (PPI) network of the DEGs and DEMs targeted genes were constructed, furthermore, Connectivity Map (CMap) database was applied to select the potential drugs with therapeutic effects.Overall, we identified 396 upregulated and 19 downregulated DEGs. Additionally, we identified 1 upregulated DEM, miR-135b, and a downregulated DEM, miR-574-5p. Functional enrichment analysis indicated that both DEGs and DEMs targeted genes participated in biological process (BP) of regulation of transcription from RNA polymerase II promoter, DNA-templated positive regulation of transcription, and Epstein-Barr virus infection signaling pathway. Besides, upregulated EP300 gene was a hub node both in DEGs and DEMs target genes. CMap database analysis indicated that sanguinarine, verteporfin, and chrysin are potential drugs for prevention and treatment of NPC metastasis.In summary, the common hub gene, biological process and pathway identified in the study provided a novel insight into the potential mechanism of NPC metastasis. Furthermore, we identified several possible small molecule compounds for treatment of NPC metastasis.