In our study, the results showed that USP21 positively regulated FOXM1 expression, and overexpression of FOXM1 could reverse the cell proliferation ability, cell migration and invasion ability, and cell stemness profiles, suggesting that USP21 promoted nasopharyngeal carcinoma progression through regulating FOXM1 expression. The gene discussed is FOXM1; the disease is nasopharyngeal carcinoma.