Understanding the mechanism by which hormone refractory prostate cancer (HRPC) develops remains a major issue. Alterations in HRPC include androgen receptor (AR) changes. In addition, the AR is activated by cytokines such as interleukin-6 (IL-6). Atypical protein kinase C (aPKClambda/iota) has been implicated in the progression of several cancers. Herein, we provide evidence that aPKClambda/iota expression correlates with prostate cancer recurrence. Experiments in vitro and in vivo revealed aPKClambda/iota to be involved in prostate cancer cell growth through secretion of IL-6. Further, aPKClambda/iota activates transcription of the IL-6 gene through NFkappaB and AP-1. We conclude that aPKClambda/iota promotes the growth of hormone independent prostate cancer cells by stimulating IL-6 production in an autocrine manner. Our findings not only explain the link between aPKClambda/iota and IL-6, implicated in the progression a variety of cancers, but also establish a molecular change involved in the development of HRPC. Further, aPKClambda/iota expression might be a biomarker for prostate cancer progression.