Colorectal cancer (CRC) is one of the main causes of death worldwide. Several factors contribute to the emergence of these tumors. At this point, the healthy microbiota has a fundamental role: maintain a protective microenvironment by preserving mucosal integrity and normal cell proliferation. In this chapter, we addressed the implications of bacterial dysbiosis on the proliferation of genotoxin-producing bacteria and tumor development. Specific attention of the role of genotoxins in the emergence of mutations may help to better understand the relationship between bacterial dysbiosis and tumor development. Bacterial dysbiosis increases the proliferation of opportunistic genotoxin-producing pathogens. For instance, colibactin and cytolethal distending toxin (CDT) produced by Escherichia coli can cause genotoxicity damage to the cell’s DNA. As dysregulation of several signaling pathways is commonly found in colon tumor cells, we discussed the genotoxicity damage in genes responsible for signaling pathways like the PI3K, MAPK, and WNT/β-catenin. Existence of several gaps regarding specific stimuli that induce mutations and the emergence of tumors by genotoxin-producing bacteria can be the subject of further investigations.