In this study, we investigated the functional and clinical significance of the long non-coding RNA (lncRNA) FAM181A-AS1 in human gliomas. TCGA, GTEx and CGGA database analyses showed that high FAM181A-AS1 expression correlates with advanced tumor stage and poor survival of glioma patients. FAM181A-AS1 expression is higher in glioma cell lines compared to normal human astrocytes (NHA). CCK-8, EdU, and colony formation assays show that FAM181A-AS1 knockdown decreases proliferation and colony formation in glioma cells, whereas, FAM181A-AS1 overexpression reverses these effects. Bioinformatics analysis showed that miR-129-5p is a potential target of FAM181A-AS1. MiR-129-5p expression negatively correlates with FAM181A-AS1 expression in glioma patients. Dual luciferase reporter assays confirmed that miR-129-5p binds directly to FAM181A-AS1 in glioma cells. RNA immunoprecipitation (RIP) assays using anti-Ago2 antibody pulled down FAM181A-AS1 with miR-129-5p. Bioinformatics analysis identified ZRANB2 as a potential miR-129-5p target gene. Dual luciferase reporter assays confirmed that miR-129-5p binds directly to the 3'-UTR of ZRANB2 mRNA. Furthermore, miR-129-5p overexpression or ZRANB2 knockdown reduces proliferation and colony formation of FAM181A-AS1 overexpressing glioma cells. These findings show that FAM181A-AS1 promotes gliomagenesis by enhancing ZRANB2 expression by sponging of miR-129-5p.