INI1/hSNF5/BAF47 is a core component of the hSWI/SNF ATP-dependent chromatin-remodeling complex. It has been suggested that INI1/hSNF5/BAF47 contributes to the regulation of many genes. In this report, we showed that the overexpression of INI1/hSNF5/BAF47 repressed c-fos promoter activity and endogenous c-fos transcription in 293T cells, and the siRNA targeting INI1/hSNF5/BAF47 (siINI1) reversed the inhibitory effect. Histone deacetylation by histone deacetylases (HDACs) was necessary for the repression of c-fos transcription by INI1/hSNF5/BAF47. HDAC and INI1/hSNF5/BAF47 functioned together to suppress c-fos transcription. ChIP experiments demonstrated that INI1/hSNF5/BAF47 could be recruited to the region of c-fos promoter to reduce histone acetylation. Altogether, these data show that INI1/hSNF5/BAF47 represses c-fos transcription via a histone deacetylase (HDAC)-dependent manner.