FZD8, a G protein-coupled receptor protein belonging to the Frizzled family, is considered to play an important role in cancer invasion and metastasis. However, the function of FZD8 in the invasion and metastasis of gastric cancer (GC) has not been elucidated. In this study, we first confirm that FZD8 protein expression was significantly upregulated in gastric cancer tissue and has a potential to be an independent predictor of poor prognosis for patients with GC. In vivo and in vitro evidences were provided that support the idea of FZD8 being able to suppress GC cell invasion and metastasis. Further studies show that FZD8 promotes the markers expression related to invasion and metastasis. FZD8 exerts biological function through the β-catenin pathway which plays an important role in invasion and metastasis of gastric cancer cells. Finally, FZD8 could activate the β-catenin pathway and its target gene's expression. In conclusion, our findings show that FZD8 promotes GC invasion and metastasis via the β-catenin pathway.,? 2020 by the Association of Clinical Scientists, Inc.