Proline rich 11 (PRR11) serves an important role in the development and progression of a number of types of human cancer. However, the clinical role of PRR11 in tongue squamous cell carcinoma (TSCC) remains unknown. The present study aimed to investigate the expression and clinicopathological significance of PRR11 in TSCC. The Cancer Genome Atlas analysis demonstrated that the upregulation of PRR11 in TSCC correlated with poor prognosis. The data of the present study revealed that PRR11 mRNA and protein expression was markedly upregulated in human TSCC tissues. Immunohistochemistry on 72 archived paraffin-embedded TSCC specimens suggested that high levels of PRR11 expression were significantly associated with clinical stage (P<0.001), T classification (P=0.009), N classification (P=0.017) and vital status (P=0.010). In addition, patients with TSCC with higher PRR11 expression exhibited substantially shorter survival times compared with patients with lower PRR11 expression (P<0.001). Univariate and multivariate analyses indicated that PRR11 upregulation may be an independent prognostic factor for patients with TSCC (P=0.001). Taken together, and to the best of our knowledge, the results of the present study demonstrated for the first time that PRR11 is involved in the development and progression of TSCC, and may serve as a useful prognostic marker and an effective target for treating TSCC.