Yin Yang 1 (YY1) plays an indispensable role in embryonic development. YY1 contains an evolutionarily conserved, 22-amino acid segment, the PHO homology region (PHR), which is located within its central domain (spacer) and has been shown previously to participate in the recruitment of Polycomb group of proteins and in YY1-mediated transcription. In this report, we show that the PHR physically interacts with several Abd-B-type Hox proteins. Although ectopic expression of Hoxa11 enhanced target promoter activity, overexpression of YY1 repressed this effect, which was abrogated by YY1 siRNA and the histone deacetylase inhibitor trichostatin A. We have further demonstrated that this suppression effect was the result of YY1-dependent recruitment of HDAC2 to the Hoxa11 target promoter. Taken together, our findings show that YY1 represses Hoxa11-dependent transcription via interactions with the Hox proteins and HDAC recruitment, providing a link between an Abd-type Hox protein and a Polycomb group protein at the level of direct protein-protein interactions. These findings not only provide a novel insight into YY1 function but also identify a new regulation of homeotic protein-mediated transcriptional regulation in general.