Glioma is the most common primary tumor in the intracranial region, accounting for more than one-half of all central nervous system tumors. Abnormal expression of key cancer genes often promotes the occurrence and development of tumors. DEP domain containing 1 (DEPDC1) is a gene that encodes a protein containing a DEP domain, which serves an important role in numerous biological processes. In the present study, the relationship between the expression level of DEPDC1 and the clinical features of glioma was explored in datasets from the China Glioma Genome Atlas Project. Kaplan-Meier survival analysis was performed to evaluate the value of DEPDC1 expression in the prognosis of patients with glioma. T-test and univariate Cox analysis were used to identify differential genes, and Gene Ontology and gene set enrichment analysis (GSEA) were used to explore the function and related mechanisms of DEPDC1 in glioma. Univariate cox and multivariate cox analyses were used to screen variables, and a nomogram model was used to construct a prediction model. In glioma U87 and LN229 cell lines, the expression of DEPDC1 was decreased using shRNA to assess the effects of DEPDC1 on the proliferation, migration and invasion of glioma cells. The findings revealed that there was a positive association between the expression level of DEPDC1 and the poor clinical features of glioma, and patients with high expression of DEPDC1 had a significantly shorter overall survival time. GSEA demonstrated that the differential genes in the DEPDC1 high expression group were mainly enriched in 'cell cycle' and 'mitotic cell cycle'. Cell experiments showed that silencing DEPDC1 in U87 and LN229 cells significantly attenuated cell proliferation, migration and invasion. To conclude, the present study demonstrates that DEPDC1 is an independent prognostic indicator for patients with glioma and is associated with a poor prognosis. The expression of DEPDC1 is closely associated with the cell cycle of glioma and provides individualized treatment options for tumors.