Colorectal cancer (CRC) is ranked third most incident and second most deadly around the world, and even though treatments significantly developed over the years, overall survival remains low. This scenario has the contribution of cancer stem cells (CSC), a subpopulation of the heterogeneous tumor bulk, considered to be responsible for the tumor maintenance, conventional therapies resistance, metastasis, and recurrence. In this regard, hypoxia appears as an important component of tumor microenvironment and CSC niche, being associated with a worse prognosis. Therefore, it is vital the study of hypoxia influence on CSC phenotype in CRC. The aim of this mini-review article is to present a brief overview on this field. Recent articles discoursed about CSC molecular regulation, signalling pathways, methods for the study of the topic, as well as molecules and drugs capacity of inhibiting the interplay of hypoxia-CSC. Finally, the studies demonstrated important results, extensively accessing the topics of cellular and molecular regulation and therapeutic intervention, being morphology an area to be more explored.