Objective：The objective of the current study was to investigate the effects of RGFP966，a histone deacetylase 3 inhibitor，on the proliferation and cell cycle of gastric cancer cells，as well as its underlying mechanism. Methods：The activity of MKN- 45 and MGC-803 cell lines treated with RGFP966 was assessed using the CCK-8 method. The cytoclonal ability of gastric cancer cells in response to RGFP966 was examined using a cell cloning assay. Flow cytometry was employed to analyze the cell cycle distribution. The protein expressions of Ki-67，c-Myc，Cyclin A2，Cyclin D1，and the PI3K/AKT signaling pathway were evaluated through Western blot analysis. Results：Compared with the control group，RGFP966 significantly inhibited the proliferation and clonal ability of MKN- 45 and MGC-803 gastric cancer cells. Flow cytometry analysis revealed that RGFP966 induced cell cycle arrest at the G0/G1 phase. Furthermore，treatment with RGFP966 resulted in reduced levels of the proliferation-related proteins Ki-67 and c-Myc，as well as decreased expressions of Cyclin A2 and Cyclin D1. Moreover，RGFP966 significantly suppressed the phosphorylation levels of PI3K and AKT. Conclusion：Our findings indicate that RGFP966 inhibits the proliferation of gastric cancer cells and induces cell cycle arrest at the G0/G1 phase. These effects may be attributed to the inhibition of the PI3K/AKT signaling pathway by RGFP966.