Nasopharyngeal cancer is one of the most common malignant tumors in the head and neck. Identification of promising miRNA biomarkers might benefit a lot to the detection of nasopharyngeal carcinoma. miRNA expression profile and clinical information were obtained from two microarray profiling data sets from the Gene Expression Omnibus (GEO) database. miRNA signature model was constructed via univariate Cox survival analysis, multivariate Cox survival analysis, and least absolute shrinkage and selection operator Cox regression analysis. Kaplan–Meier curve, area under the curve (AUC), decision curve analysis, Box plot, and nomogram were used to evaluate the prognosis of the model to patients. 67 up-regulated and 93 down-regulated miRNAs were identified from GEO microarray data sets ( P < 0.05). A three-miRNA signature (has-miR-142-3p, has-miR-29c, and has-miR-30e) was obviously associated with the overall survival of nasopharyngeal carcinoma patients ( P < 0.001). The AUCs for the signature were 0.74, 0.7 for the training set and external validation set. The AUC of disease free survival and distant metastasis-free survival were also high. The model has better clinical independence and has better clinical prediction effect when combined with clinical characteristics ( P < 0.0001). Compared with the published models, our model had a higher AUC. Our results revealed that a three-miRNA signature was a potential novel prognostic biomarker for nasopharyngeal carcinoma. Impact statement Nasopharyngeal cancer is one of the most common malignant tumors in the head and neck. Identification of promising miRNA biomarkers might benefit a lot to the detection of nasopharyngeal carcinoma. A three-miRNA signature (has-miR-142-3p, has-miR-29c, and has-miR-30e) was obviously associated with the overall survival of nasopharyngeal carcinoma patients. The model has better clinical independence and has better clinical prediction effect when combined with clinical characteristics. Our results revealed that a three-miRNA signature was a potential novel prognostic biomarker for nasopharyngeal carcinoma.