Objective: To investigate the correlation between the expression of integrin binding sialoprotein (IBSP) in glioma and the clinical prognosis of patients and its regulatory effect on tumor cell proliferation, invasion and chemotherapy resistance. Methods: A public database was used to analyze the expression of IBSP in glioma and its relationship with the prognosis of patients. Knockdown and overexpression of IBSP in glioma cells, functional assays to assess cell proliferation, invasion, and chemoresistance alterations. Results: Database analysis showed that the expression level of IBSP in glioma was significantly increased, and the high level of IBSP indicated a poor prognosis. Knockdown of IBSP inhibited glioma proliferation, invasion and chemoresistance, and overexpression of IBSP promoted glioma proliferation, invasion and chemoresistance. Overexpression of IBSP promotes the activation of NF-κB pathway and the expression of downstream genes of NF-κB, which in turn promotes the malignant phenotype of glioma cells. Conclusion: IBSP promotes glioma cell proliferation, invasion and chemoresistance by activating the NF-κB signaling pathway, suggesting that IBSP can be used as a potential therapeutic target for glioma.