Abstract: Given the severe situation in gastrointestinal cancerprevention and control, the incidence and mortality rates of gastrointestinal cancer in China have been reported to be very high. Moreover, due to the weak awareness of early screening, most patients with gastrointestinal cancers are diagnosed at advanced stages. With the advocacy and development of precision medicine in recent years, precision treatment of tumors, including breast cancer, lung cancer, melanoma, and lymphoma, has made great progress. However, precision medicine for gastrointestinal tumors is relatively backward owing to challenges in signature profiling, including high heterogeneity, few molecular targets, lack of preclinical research models, and difficulties in accurate efficacy monitoring and evaluation. Therefore, our team has established an integrated research system for the precision treatment of gastrointestinal tumors over the years, covering patients’ sample database, preclinical drug evaluation platform, clinical transformation research platform, and accurate dynamic monitoring model of clinical efficacy. Notably, this system has realized the two-way transformation research mode of “clinical problems transfer into preclinical research platform” and “preclinical results return to clinical research”, which directly promote the development of precision treatment for gastrointestinal tumors. This review discusses our transformation research system, its successful application in gastrointestinal tumor cases, and its future direction of development.