Accumulating evidence has indicated the crucial role of microRNA-196 in mediating tumor progression, while its significance in cholangiocarcinoma (CCA) remains unclear. In this study, we provided the first evidence that the expression level of miR-196-5p is elevated in both CCA cell lines and clinic specimen. MiR-196-5p inhibition notably suppressed cell proliferation as well as metastasis in CCA cell line HuCCT1. Furthermore, the interaction between miR-196-5p and its downstream molecule HAND1 was verified. Moreover, a series of rescue assay verified that both HAND1 and β-catenin silencing could reverse the abnormal elevated cell proliferation and migration brought by miR-196-5p elevation, indicating that HAND1/Wnt/β-catenin signaling pathway activation is essential for miR-196-5p to exert its roles. In summary, we successfully depict the oncogenic role of miR-196-5p in promoting cell proliferation and migration in CCA via HAND1/Wnt/β-catenin axis.