Glioma-initiating cells (GICs) are implicated in tumor heterogeneity and therapeutic resistance of GBM. Here we demonstrate that the BRG1 subunit of the SWI/SNF chromatin remodeling complex plays critical roles in maintaining GICs in a stem-like state. Furthermore, we have identified a novel mechanism by which BRG1 regulates expression of TXNIP, which is a redox regulator and also negatively regulates glycolysis. We found that BRG1 regulates TXNIP through a STAT3-dependent pathway. We demonstrate that BRG1 plays a critical role in the drug resistance of GICs, and in GIC-induced tumorigenesis. Thus, the BRG1-STAT3-TXNIP axis is a potential therapeutic target in GBM.