The transcription factor CCAAT enhancer-binding protein alpha (C/EBPalpha) is a tumor suppressor in myeloid cells and inhibits proliferation in all cell types examined. C/EBPalpha interacts with the SWI/SNF chromatin-remodeling complex during the regulation of differentiation-specific genes. Here we show that C/EBPalpha fails to suppress proliferation in SWI/SNF defective cell lines after knock-down of SWI/SNF core components or after deletion of the SWI/SNF interaction domain in C/EBPalpha, respectively. Reconstitution of SWI/SNF function restores C/EBPalpha-dependent proliferation arrest. Our results show that the anti-proliferation activity of C/EBPalpha critically depends on components of the SWI/SNF core complex and suggest that the functional interaction between SWI/SNF and C/EBPalpha is a prerequisite for proliferation arrest.