The Wnt/β-catenin signaling pathway is involved in many cellular physiological processes, including embryonic development, cell proliferation and differentiation, tissue homeostasis and regeneration, etc. Aberrant activation of Wnt/β-catenin signaling is one of the most typical features in the development and progression of cancer. Abnormal accumulation of β-catenin, a core component of the Wnt/β-catenin signaling pathway, is one of the main factors leading to abnormal activation of the Wnt/β-catenin signaling pathway. Therefore, β-catenin has become an important target for the development of anticancer drugs. Some β-catenin small molecule inhibitors have been shown to have the potential to treat cancer, such as the specific β-catenin/CBP antagonist PRI-724, which has entered phase I/II clinical trials. However, the development and application of β-catenin inhibitors are still challenging due to their selectivity, specificity and physicochemical properties, etc. This review introduces the Wnt/β-catenin signaling pathway, focuses on the research progress of β-catenin small molecule inhibitors, and prospects for the development of drug in the future.