Abstract: Tumor stem cells have the property of continuous self-renewal and multi-directional differentiation, which are the main causes of tumor recurrence and drug resistance. Whether the tumor stem cells can be accurately identified and targeted for destruction has become a new direction and hot topic in the research of oncology. The transmembrane protein Lgr5 is widely expressed in the digestive tract and has extremely strong stem cell activity. In addition, it has the characteristics of high specific expression on the membrane surface of gastrointestinal malignant tumors. In-depth understanding of the molecular characteristics of Lgr5 protein will help improve the sorting efficiency of gastrointestinal tumor stem cells, which is of great significance for further research on the occurrence and development mechanism of gastrointestinal tumors, exploration of new therapeutic methods, and improvement of the overall prognosis. Based on the structural characteristics of Lgr5 protein, in combination with the signal transduction pathways and the biological activity characteristics of different gastrointestinal tumors, this paper reviews the latest progress of the Lgr5 protein as a stem cell marker in the basic research field of gastrointestinal tumors in recent years, so as to provide theoretical foundation for further research.