Our observations demonstrate a reverse Warburg effect in human colorectal cancer stem cells (CRCSCs) because the expression levels and activity of hypoxia‐inducible factor‐1α are markedly increased by LRH‐1 upregulation resulted from GATA6 overexpression in the majority of colorectal cancer (CRC) cells which undergo aerobic glycolysis to proliferate rapidly and, in the meantime, generate large amount of lactate that can be uptaken by another subset of CRC cells for mitochondrial oxidative phosphorylation. Here, GATA6 is linked to colorectal carcinoma.