The human herpesvirus-associated ubiquitin-specific protease (HAUSP) deubiquitinating enzyme has been shown to regulate many proteins involved in the cell cycle, as well as tumor suppressors and oncogenes. However, the expression pattern of HAUSP in glioma patients is still unclear. The purpose of the present study was to investigate the expression pattern and prognostic significance of HAUSP in patients with glioma. Eighty glioma specimens and 10 normal control samples were obtained. Immunohistochemical assay, quantitative real-time PCR and western blot analysis were carried out to explore the expression of HAUSP. Additionally, the association of HAUSP expression with clinicopathological parameters and the survival of glioma patients were analyzed. Our results showed that HAUSP expression levels were increased from grade I to grade IV in the tumors of the glioma patients. Moreover, the survival rate of patients with HAUSP-positive tumors was lower when compared to that of patients with HAUSP-negative tumors. We further confirmed that high expression of HAUSP was a significant and independent prognostic indicator in glioma by multivariate analysis. Our data provide convincing evidence for the first time that the overexpression of HAUSP at the gene and protein levels is correlated with poor outcome in patients with glioma in China. HAUSP may play an important oncogenic role in glioma progression, and it is a potential diagnostic and therapeutic target.