BAF chromatin remodeling complexes containing the BRG1 protein have been shown to be not only essential for early embryonic development, but also paramount in enhancing the efficiency of reprogramming somatic cells to pluripotency mediated by four transcription factors. To investigate the role of BRG1 in regulating pluripotency, we found that Oct4 and Nanog levels were increased immediately after BRG1 knockdown. While Nanog levels remained elevated over the investigated time period, Oct4 levels decreased at later time points. Additionally, OCT4 target genes were also found to be upregulated upon Brg1 knockdown. SiRNA-mediated BRG1 knockdown in embryonic stem (ES) cells led to Oct4 and Nanog upregulation, whereas F9 cells showed primarily Oct4 upregulation. BRG1 knockdown upregulated the expression of differentiation markers in mouse ES cells as well as differentiated morphology under reduced leukemia inhibitory factor conditions. Our results show that BRG1 plays an important role in maintaining pluripotency by fine-tuning the expression level of Oct4 and other pluripotency-associated genes.