Abstract: Objective To investigate the inhibitory effect of synthetic I2PP2A short interfering RNA (siRNA) on the proliferation and migration of human gastric cancer cell line BGC-823 and to explore the possible molecular mechanisms. Methods The siRNA targeted I2PP2A shRNA was transfected into BGC-823 cells by LipofectamineTM 2000. Expression of I2PP2A mRNA and protein were examined by Real-time RT-PCR and Western blot, respectively. WST-1 and Transwell chamber were used to observe the proliferation and migration of BGC-823 cells, respectively. The expression of cyclin D1 and MMP-9 protein were also detected by Western blot. Results I2PP2A siRNA significantly inhibited the expression of I2PP2A in gastric cancer cell line BGC-823 at both mRNA and protein levels. Downregulated I2PP2A expression greatly inhibited the proliferation and migration of BGC-823 cells and also down-regulated the expression of cyclin D1 and MMP-9 proteins. Conclusion Down-regulated- I2PP2A-expression-mediated inhibition on the proliferation and migration of gastric carcinoma cells may be closely associated with the decreased expression of cyclin D1 and MMP-9 proteins, indicating a new approach of gene therapy for gastric cancer.