The gut microbiota is considered as a forgotten organ in human health and disease. It maintains gut homeostasis by various complex mechanisms. However, disruption of the gut microbiota has been confirmed to be related to gastrointestinal diseases such as colorectal cancer, as well as remote organs in many studies. Colorectal cancer is a multi-factorial and multi-stage involved disorder. The role for microorganisms that initiate and facilitate the process of colorectal cancer has become clear. The candidate pathogens have been identified by culture and next sequencing technology. Persuasive models have also been proposed to illustrate the complicated and dynamic time and spatial change in the carcinogenesis. Related key molecules have also been investigated to demonstrate the pathways crucial for the development of colorectal cancer. In addition, risk factors that contribute to the tumorigenesis can also be modulated to decrease the susceptibility for certain population. In addition, the results of basic studies have also translated to clinical application, which displayed a critical value for the diagnosis and therapy of colorectal cancer. In this review, we not only emphasize the exploration of the mechanisms, but also potential clinical practice implication in this microbiota era.