Abstract: Objective To investigate the role of tumor necrosis factor α induced protein 3 (TNFAIP3) in the proliferation, invasion, and migration of glioblastoma (GBM) cells and its underlying mechanisms. Methods The GEPIA database was used to analyze the mRNA levels of TNFAIP3 in GBM and its impact on patient survival. The effect of silencing or overexpressing TNFAIP3 on the proliferation, invasion, and migration of GBM cells were assessed by CCK-8 assay, colony formation assay, and cell invasion and migration assays. Furthermore, bioinformatics analysis and Western blot were employed to explore the mechanisms by which TNFAIP3 regulates the proliferation, invasion, and migration of GBM cells. Results TNFAIP3 mRNA was significantly up-regulated in GBM and associated with poor prognosis. Silencing TNFAIP3 inhibited the proliferation, invasion, and migration adilities of GBM cells, while overexpressing TNFAIP3 enhanced these abilities. Further analysis indicated that TNFAIP3 might promote the proliferation, invasion, and migration GBM cells by activating the JAK tyrosine protein kinase 2(JAK2)-signal transduction and transcription activator 3 (STAT3) signaling pathway. Conclusions TNFAIP3 is highly expressed in GBM and promotes the proliferation, invasion, and migration of GBM cells through the activation of the JAK2-STAT3 signaling pathway.