Background: Glioblastoma (GBM) is a malignant brain tumor with poor prognosis. However, the potential pathogenesis and therapeutic target s still needs to be explored.Methods: Herein, The Cancer Genome Atlas (TCGA) expression profile data and clinical information were downloaded, and the Weighted Gene Co-expression Network Analysis (WGCNA) was conducted. Subsequently, hub genes which closely related to the poor prognosis of GBM were obtained. Further, the relationship between the genes of interest and prognosis of GBM patients, and immune microenvironment were analysed. Patients from TCGA were divided into high- and low-risk groups.Results: Top 10 hub genes (CDC20, NCAPH, CDCA5, BUB1, CDCA8, PBK, KIF2C, TPX2, TTK and TOP2A) were obtained. Then, we performed single-gene analysis on CDCA5 and CDCA8 as genes of interest. We found that their expression levels were closely related to overall survival (OS). They had good correlations with the genes that regulate cell cycle in p53 signaling pathway. Moreover, it revealed that high amplication of CDCA5 was correlated with CD8 + T cells while CDCA8 with CD4 + T cells, and the expression of these two genes showed a significant difference in OS.Conclusions: These results might provide new molecular targets and intervention strategy for GBM.