We found that JmjC-domain containing histone demethylase 2B (JMJD2B), which is induced by ETBF in a Toll-like receptor (TLR) 4-nuclear factor of activated T-cells 5 (NFAT5)-dependent manner, plays an important role in the stemness of human CRC cells, which could promote the expression of NANOG by binding and removing the inhibitory H3K9me3 marks on the NANOG promoter region. The gene discussed is NANOG; the disease is colorectal carcinoma.