There are currently few successful therapies for castration-resistant prostate cancer (CRPC). CRPC is thought to result from augmented activation of the androgen/androgen receptor (AR) signaling pathway, which could be enhanced by AR cofactors. In this study, heterochromatin protein 1b (HP1b), but not HP1a or HP1g was found to be an AR cofactor. HP1b interacted with the AR, and enhanced the DNA-binding ability of AR to androgen-responsive element in the prostate-specific antigen enhancer and promoter regions, and to increase the transcription of AR target genes. In prostate cancer (PCa) tissues, HP1b expressions correlated with Gleason score and tri-methylation levels of histone H3 lysine 9. Silencing of HP1b suppressed the growth of AR-expressing PCa cells by inducing cell-cycle arrest at the G 1 phase, similar to inhibition of androgen/AR signaling. Furthermore, HP1b was overexpressed in castration-resistant LNCaP derivative CxR cells, and HP1b knockdown also suppressed the cell growth in CxR cells. These findings indicate that HP1b is involved in the proliferation of AR-expressing PCa cells and progression to CRPC as an AR coactivator. Modulation of HP1b expression or function might be a useful strategy for developing novel therapeutics for PCa, even in CRPC.