Colorectal cancer is one of the most often diagnosed malignant tumors in humans. Undoubtedly, dietary patterns and lifestyle are strongly implicated in the pathogenesis of sporadic colorectal cancer. Evidence is emerging for the participation of human gut microflora in the pathogenesis of colorectal cancer. Chemoprevention of colorectal cancer with medications is an attractive opportunity, although the results from clinical trials are inconclusive. This review discusses the association between the colorectal cancer and some of the most important dietary and lifestyle risk factors, as well as the role of gut microbiota and chemoprevention with acetylsalicylic acid in colorectal cancer.