Colorectal cancer is a global public health issue which possesses serious challenge. The incidence of colorectal cancer in developed countries and regions stands in the forefront worldwide, and has been rising sharply in some of the developing countries. It is unanimously recognized that the occurrence of colorectal cancer is closely related to environmental factors as diet and lifestyle, genetic factors, and gene-environment interactions of the people. Since there have been many studies on the influencing factors of colorectal cancer, the current review aims at providing evidence on colorectal cancer prevention by evaluating the relationships between the influencing factors and colorectal cancer, based on the published literatures. Environmental risk factors revealed by previous epidemiological studies facilitate the population-based prevention programs against colorectal cancer. The developments of sequencing and omics technologies provide more chances to illustrate the genetic susceptibility of colorectal cancer. With both, we are able to construct more accurate risk prediction models and subsequently developing personalized intervention plans to achieve the ultimate goal of reducing the burden of colorectal cancer.