Liver-intestine cadherin (CDH17) represents a novel type of cadherin within the cadherin superfamily, and is distinguished from other cadherins by its distinct structural and functional features. Our previous studies had identified that increased CDH17 was significantly associated with tumor differentiation and lymph node metastasis in gastric cancer. In this study, we tested the hypothesis that CDH17 was associated with proliferation and invasiveness in gastric cancer using recombinant lentivirus-mediated miRNA targeting to CDH17 both in vitro and in vivo. We also detected the activity of matrix metalloproteinase (MMP)-2 and MMP-9 with gelatin zymography to explore the mechanisms underlying the inhibition of the CDH17 gene. Our results showed that a well-differentiated gastric cancer cell line had higher CDH17 expression. Down-regulation of CDH17 inhibited proliferation, adherence, and invasion of the poorly differentiated BGC823 gastric cancer cells in vitro, and induced cell cycle arrest. The activities of MMP-2 and MMP-9 were lower in the CDH17-miRNA-transfected cells compared to the control cells. Using an in vivo tumor growth assay, we confirmed that CDH17 silencing could obviously slow the growth of gastric cancer derived from BGC823 cells. Taken together, we have demonstrated that CDH17 maybe a positive regulator for proliferative, adhesive, and invasive behaviors of gastric cancer.