We found that rs34533650 in EPAS1 was associated with colorectal cancer risk (OR = 1.43, 95% CI = 1.20–1.70, P(FDR) = 8.35 × 10−4), and this finding was validated in two independent populations (Japanese: OR = 1.07, 95% CI = 1.01–1.15, p = 3.38 × 10−2; European: OR = 1.11, 95% CI = 1.03–1.19, p = 6.04 × 10−3). This evidence concerns the gene EPAS1 and colorectal cancer.