Abstract: Hypoxic microenvironment is a typical characteristic of solid tumors and is considered an independent risk factor in tu -mor progression and poor prognosis. Hypoxic microenvironment is a critical part of cancer stem cell (CSC) niche and plays an impor-tant role in the evolution of cancer stem cells in tumors and in apoptosis resistance. As a key factor in the tumor's adaption to hypoxic microenvironment, hypoxia inducible factors (HIFs) can induce biological behavioral changes in CSCs that can accelerate tumor malig-nant transformation. Such behavioral changes include anti-apoptosis, enhancement of drug-resistance gene expression, and tumor inva-sion and metastasis. HIFs are also among the main factors affecting the capacity of CSCs to maintain their biological characteristics. In this review, the authors focus on recent advances in our understanding of the role that HIFs play in maintaining the biological characteristics of CSCs.