In this study, we focused on the regulation of CD133 by HIF-1α and HIF-2α, and demonstrated that 1) HIF-1α and HIF-2α upregulate CD133 promoter activity, particularly of P5, 2) HIF-1α and HIF-2α bind to the proximal CD133 P5 promoter at EBS, 3) HIF-1α physically interacts with Elk1, and 4) expression of CD133 is regulated by HIF-1α and HIF-2α in colon cancer cells. This evidence concerns the gene PROM1 and malignant colon neoplasm.