Our results showed that IL-8 regulates the CXCR2 receptor to promote the activation of the PI3K/AKT signaling pathway, sustain CD97 expression, and facilitate upregulation of the mesenchymal markers N-cadherin and vimentin, which are indispensable driving forces for ICC metastasis. This evidence concerns the gene CDH2 and intrahepatic cholangiocarcinoma.