Objective To investigate the expression of HOPX in gastric cancer and the ability to regulate the proliferation of gastric cancer cells and its mechanism. Methods HOPX expression in gastric cancer cells and tissues were detected by Real⁃Time PCR and Western Blot. CCK⁃8，colony formation，EdU and flow cytometry assays were performed to investigate the tumor suppressor gene functions of HOPX in the growth and proliferation capability of gastric cancer cells. In addition，TOP flash and FOP flash plasmids were transfected into gastric cancer cells， and the effect of HOPX on the transcriptional activity of β ⁃catenin/TCF/LEF was detected by luciferase reporter assay. Furthermore，the effect of HOPX on the expression of GSK⁃3β，p⁃GSK⁃3β and β⁃catenin in gastric cancer cells was detected by Western blot. In order to explore the mechanism of gastric cancer cell proliferation mediated by HOPX，we further detected the expression level of β⁃catenin protein in gastric cancer nucleus and the expres⁃ sion of downstream target gene CyclinD1. Results Real time ⁃PCR and Western blot showed that the expression levels of mRNA and protein of HOPX in gastric cancer were significantly decreased，and the overexpression of HOPX significantly inhibited the proliferation and G1⁃S phase cell⁃cycle transition of gastric cancer cells. Western blot results show that overexpression of HOPX can promote the degradation of β⁃catenin by inhibiting the phosphor⁃ ylation level of GSK3β，thus inhibit the entry of β⁃catenin into the nucleus，and then down⁃regulate the expression of downstream target gene CyclinD1，so as to inhibit the proliferation of gastric cancer cells. Conclusion This study found that overexpression of HOPX inhibits the proliferation of gastric cancer cells by inhibiting Wnt/β⁃catenin signaling pathway.