Abstract: Objective To explore the role of endothelin-1 (ET-1) gene in regulating the proliferation, migration and invasion of nasopharyngeal carcinoma cells. Methods A lentivirus-mediated shRNA-ET-1 vector was infected into 5-8F cells, and the interference efficiency was examined with Western blotting. MTT assay, cell cycle analysis, plate colony formation assay, Transwell assay, Boyden chamber assay and tumor growth assay were carried out to analyze the changes in cell proliferation, migration and invasion. The expressions of genes related with epithelial-mesenchymal transition (EMT) were examined using Western blotting. Results shRNA-ET-1 transfection significantly inhibited the expression of ET-1, and suppressed the growth, migration and invasion of 5-8F cells. ET-1 knockdown enhanced the expression of E-cadherin and CK18 and inhibited the expression of N-cadherin and vimentin. Conclusion ET-1 promotes cell growth, migration and invasion by modulating the genes associated with epithelial-mesenchymal transition in nasopharyngeal carcinoma cells.