Background: The cell division cycle-associated protein 2 (CDCA2) was found to be a cell cycle-related protein. CDCA2 was previously reported to be associated with proliferation and migration in multiple cancer. We evaluated the role of CDCA2 in glioma using publicly available data from the Chinese Glioma Genome Atlas (CGGA) and The Cancer Genome Atlas (TCGA).Methods: The relationships between clinical characteristics and CDCA2 expression were analyzed using the Wilcoxon test or Kruskal-Wallis test. Clinicopathologic characteristics associated with overall survival (OS) were analyzed using Cox regression analysis and Kaplan-Meier method. Gene Set Enrichment Analysis (GSEA) was performed to sort the signaling pathway associated with the expression of CDCA2. Pearson correlation test was used to analyse the expression correlation between CDCA2 and well-known cell cycle-related genes.Results: Glioma with high CDCA2 expression was more prone to be associated with advanced malignancy clinical pathologic characteristics and worse prognosis than that with low CDCA2 expression in TCGA and CGGA dataset (P < 0.001). The multiple analysis revealed that CDCA2 was independently associated with OS (HR:1.396; [CI]:1.236 − 1.577, P < 0.001). GSEA showed that cell cycle checkpoint, cell cycle G1/S phase transition, DNA damage checkpoint and regulation of cell cycle arrest were enriched in CDCA2 high expression phenotype. Pearson correlation test revealed that CDCA2 was co-expression with well-known key cell cycle-related genes (CCNA2, CCNB1, CCNB2, CCNE1, CCNE2, CDK1, CDK2, CDK4, CDK6).Conclusion: High CDCA2 expression may be a potential prognosis molecular marker of poor survival in glioma. Cell cycle regulation pathway may be the key pathway regulated by CDCA2 in glioma.