Colorectal cancer (CRC) is the fourth most common cancer in 2018 with poor prognosis. Fusobacterium nucleatum (F.n), an anaerobe, is found to be enriched in both stools and tumor tissues of CRC patients. As surveys show, tumor initiates before the collection of F.n. In return, F.n helps cancer cells to build up tumor microenvironment and benefit for their chemo-resistant. The elements constituted the tumor environment, including neutrophils, macrophages and lymphocytes, contribute to the existing of tumor cells respectively. However, the integrated and interactive roles of those elements are poorly investigated. The intracellular molecular alteration MSI is a result of F.n infection and the microbiology-molecular pathological epidemiology (MPE) has become a new trend to analysis F.n and tumorigenesis. Chemoresistance of tumor cells is also affected by F.n induced microenvironment, or F.n achieves it directly. Finally, F.n could be a biomarker of CRC. All in all, our review will lay a foundation for the therapy of CRC through the interference of F.n and perspective to follow-up studies.