Gliomas account for 75% of all primary malignant brain tumors in adults and are associated with high mortality. Mounting evidence has shown that NCAPG2 is differentially expressed in various cancers. However, the prognostic value and immune functions of NCAPG2 in low-grade glioma (LGG) remain unresolved. In the present study, we revealed that NCAPG2 was up-regulated in LGG, and its higher expression was associated with adverse clinical outcomes and poor clinical characteristics, including WHO grade, IDH mutation, 1p/19q codeletion, and primary therapy outcome. The results of the Cox regression analysis revealed that NCAPG2 was an independent factor for the prognosis of low-grade glioma. Meanwhile, we also established a nomogram based on NCAPG2 to predict the 1-, 3-, or 5-year survival in LGG patients. Furthermore, we found that Copy number variation (CNV) and DNA hypomethylation results in its overexpression in LGG. In addition, functional annotation confirmed that NCAPG2 was mainly involved in the immune regulation and WNT signaling pathways. Finally, we determined that increased expression of NCAPG2 was correlated with infiltration levels of various immune cells and immune checkpoint in LGG. Importantly, we found that NCAPG2 was highly expressed in glioma stem cells lines and knockdown of NCAPG2 significantly inhibited the self-renewal ability of GSC. This is the first study to identify NCAPG2 as a new potential prognostic biomarker and characterize the functional roles of NCAPG2 in the progression of LGG, and provides a novel potential diagnostic and therapeutic biomarker for LGG in the future.Copyright © 2022 Ren, Yang, Chen, Guo, Zhao, Yang, Nie, Ding and Zhang.