Gender difference in the incidence of colorectal cancer is well known and has been supported by various epidemiologic studies. In Korea, women have lower incidence of colorectal cancer and adenoma, and the incidence in men has recently increased. Hormone replacement therapy in menopausal women is preventive of colorectal cancer but can cause cardiovascular diseases and breast cancer. Estrogen exerts diverse effects through estrogen receptors, ERα and ERβ. ERβ is associated with anti-proliferation and apoptosis. The ratio of ERα/ERβ is important in the protection and tumorigenesis of colorectal cancer. Therefore ERβ modulation has been investigated for preventing or treating colorectal cancer and avoiding adverse effects of estrogen at the same time. In addition, the gender-difference in the incidence of colorectal cancer should be taken into account when making guidelines on colorectal surveillance for Korean population.