Hepatocellular carcinoma-related protein 1 (HCRP1), also known as the homologue of vacuolar protein sorting 37A (hVps37A), serves as a membrane trafficking complex to mediate internalization and degradation of ubiquitinated membrane receptors. Recently, more and more researchers have showed that HCRP1 plays a critical role in tumorigenesis. However, the biological roles of HCRP1 in glioma remain to be elucidated. In the present study, we detected the expression pattern of HCRP1 in glioma. The results showed that HCRP1 was significantly down-regulated in glioma tissues and cell lines. On the basis of further analysis, we demonstrated that up-regulation of HCRP1 efficiently inhibited glioma cell proliferation and invasion in vitro, and as well as suppressed glioma cell growth in vivo. In addition, we found that HCRP1 up-regulation decreased the levels of p-ERK and p-AKT in glioma cells. We also emphasized that the ERK and AKT signaling pathways were the mechanisms underlying the inhibitory effect of HCRP1 on glioma cells. Taken together, we provided evidence in support of the prognostic value of HCRP1 in glioma and suggested it as a promising target for glioma treatment.