By transcriptome sequencing (RNA sequencing, RNA‐Seq) and bisulfite post‐transformation polymerase chain reaction (BSP), we demonstrated that TET1 relies on its catalytic activity to target the claudin‐3 (CLDN3) promoter region for demethylation, thereby promoting its transcription and consequently promoting epithelial‐to‐mesenchymal transition (EMT) in CCA. This evidence concerns the gene CLDN3 and cholangiocarcinoma.