Colon holds a complex microbial community, which is crucial for maintaining homeostasis and regulating metabolic functions, supporting the intestinal barrier and controlling immune responses. Previous studies have supported a link between intestinal microbiota and colorectal cancer (CRC). Based on these fndings, the present review analyzed the numerous interactions that occur between microbiota and CRC, starting from the role of intestinal microbiota in colonic homoeostasis. Intestinal microbiota is a cause of CRC and involves various mechanisms such as chronic inflammation, the production of genotoxins causing DNA impairment and/or the biosynthesis of toxic compounds. Moreover, basic metabolic factors such as short-chain fatty acids (SCFAs) and bile acids are included in CRC pathogenesis. Different pathogenic pathways have been reported among different CRC regions (proximal or distal). Variations in the microbial populations are reported between the CRC from these colonic sites, possibly reflecting the bacterial dysbiosis and bioflm distribution. Bowel preparation is essential prior to colonoscopy and surgery; there is, however, minor consensus on the effects of this procedure on intestinal microbiota, notably with regard to the long-term outcomes. With regard to the therapeutic strategy in CRC, the intestinal microbiota is further involved in the modulation of the host response to chemotherapeutic agents (5-fluorouracil and irinotecan) by the interference with drug efcacy and by adverse effects and associated toxicity. In addition, the newly emerged research on CRC immunotherapy reveals an important interplay between intestinal microbiota and the immune system, which includes the possibility of targeting microbiota for the enhancement of anticancer treatment. Additional studies will further clarify the interaction between microbiota and CRC, resulting in the development of alternative therapeutic strategies by manipulating microbiota composition.