Abstract: In the past, antioncogene-oncogene interaction was considered as a major mechanism in colorectal cancer development. However, recently, microsatellite instability was found to be another important mechanism in colorectal cancer, especially hereditary non-polyposis colorectal cancer. These patients usually have unique clinicopathologic features, such as poorly differentiated adenocarcinoma on the right side, mucinous colon cancers, and abundance of tumor-infiltrating lymphocytes. Chemotherapy is a major postoperative therapeutic method, and fluorouracil-based chemotherapy is the foundation of chemotherapy in colorectal cancer patients. Thus, the sensibility of the fluorouracil plays an important role in the treatment of colorectal cancer patients and has become a popular research topic. Recently, some scholars have suggested that microsatellite instability and other biological molecular markers can predict the sensibility of chemotherapy and the prognosis of colorectal cancer patients. Thus, microsatellite instability may be a good prognostic factor and indicator of chemotherapy response. It can also be a theoretical evidence for individual treatment of cancer. However, clinical trials with larger tissue samples are needed to confirm the above findings.