Fibroblast growth factor receptor (FGFR) family includes four highly conserved receptor tyrosine kinases. Particularly, FGFR2 has been identified as a potential target for tyrosine kinase inhibitor (TKI) treatment. Except for immunohistochemistry and fluorescence in situ hybridization, next-generation sequencing (NGS) technology represents a novel tool for FGFR2 detection that covers a wide range of fusion genes. In the present work, we present a case of cholangiocarcinoma who had FGFR2-BICC1 rearrangement detected by NGS. A 76-year-old female diagnosed with cholangiocarcinoma underwent four cycles of chemotherapy. The NGS assay showed that the tumor had a FGFR2-BICC1 rearrangement. The patient had a favorable tumor response to sorafenib. Herein, we report the first case with cholangiocarcinoma harboring FGFR2-BICC1 who is sensitive to sorafenib therapy.