Chromium (Cr) is widely used in industry, making its toxicity a matter of concern. Although hexavalent Cr [Cr (VI)] can promote cancer cell proliferation in several cancers, there is little evidence implicating Cr(VI) in cancer cell migration, especially in prostate cancer. We show that the Cr concentration is higher in the serum of prostate cancer patients, and is closely associated with unfavorable outcomes for the patients. Additionally, low dose trivalent Cr [Cr(III)] exposure has no obvious carcinogenic effects in prostate cancer. However, Cr(VI) can promote proliferation and invasion of prostate cancer cell line PC3 cells in vitro and in vivo. In seeking the molecular mechanism of Cr(VI) exposure on cancer progression, we found that Cr(VI) could down-regulate the epithelial protein marker, E-cadherin, and up-regulate mesenchymal protein markers, such as N-cadherin and Snail. Together, these data indicate that Cr(VI) is a newly verified carcinogen in prostate cancer, and can promote cell migration by affecting the Epithelial-Mesenchymal Transition (EMT) pathway. Thus, inhibition of Cr (VI)-EMT signaling is a prospective approach toward limiting prostate tumor progression.