In our work, dose‐dependent cell cycle arrest in G0/G1 phase was obvious in ICC cell lines after treatment with lenvatinib, which was consistent with the observed levels of important proteins involved in the cell cycle, including CDK1/CyclinB1 and CDK2/Cyclin E. Based on transcriptome analysis, we found that Gadd45a was significantly upregulated after treatment with lenvatinib. Here, CDK2 is linked to intrahepatic cholangiocarcinoma.