Abstract: CD133 is one of the well-known markers of cancer stem cell (CSC), and also a functional molecule that can regulate the occurrence and development of tumors, participating in tumor recurrence, metastasis, drug resistance and other processes. CD133 protein has an effect on tumor angiogenesis, hypoxia, epithelial-mesenchymal transition (EMT) and other aspects by activating Wnt/β-catenin, PI3K-AKT and other signaling pathways, thus resulting in an enhancement in tumor cell characterization and drug resistance. This article analyzes the relationship between CD133 protein and tumor from the aspects of CD133's influence on tumor related angiogenesis, hypoxia regulation, mediating EMT process, immune microenvironment, regulatory pathway, targeted therapy, etc., discusses the controversy of CD133 as a CSCs marker, and summarizes its mechanism of regulating tumor cells and its value as a new potential target of tumor.