Nuclear pore complex (NPC) is a major transport pivot for nucleocytoplasmic molecule exchange. Nucleoporin 205 (NUP205)—a main component of NPC—plays a key regulatory role in tumor cell proliferation; however, few reports document its effect on the pathological progression of lower-grade glioma (LGG). Therefore, we conducted an integrated analysis using 906 samples from multiple public databases to explore the effects ofNUP205on the prognosis, clinicopathological characteristics, regulatory mechanism, and tumor immune microenvironment (TIME) formation in LGG. First, multiple methods consistently showed that the mRNA and protein expression levels ofNUP205were higher in LGG tumor tissue than in normal brain tissue. This increased expression was mainly noted in the higher WHO Grade, IDH-wild type, and 1p19q non-codeleted type. Second, various survival analysis methods showed that the highly expressedNUP205was an independent risk indicator that led to reduced survival time of patients with LGG. Third, GSEA analysis showed thatNUP205regulated the pathological progress of LGGviathe cell cycle, notch signaling pathway, and aminoacyl-tRNA biosynthesis. Ultimately, immune correlation analysis suggested that highNUP205expression was positively correlated with the infiltration of multiple immune cells, particularly M2 macrophages, and was positively correlated with eight immune checkpoints, particularly PD-L1. Collectively, this study documented the pathogenicity ofNUP205in LGG for the first time, expanding our understanding of its molecular function. Furthermore, this study highlighted the potential value ofNUP205as a target of anti-LGG immunotherapy.