Update publication. In this study, we found that CB inhibited ICC cell proliferation and promoted cell apoptosis. By using phosphoproteomics, we found significant changes in the proteome and phosphorylome associated with DNA damage and apoptosis in response to CB treatment. Further investigations demonstrated that CB induced ICC cell apoptosis by activating the ATM/CHK2/p53 signaling pathway and upregulating the expression of Fas, DR4 and DR5. Our results collectively indicate that CB may serve as a potential anti-cholangiocarcinoma drug