Objective To investigate the expression and clinical significance of Sonic hedgehog(Shh), Glioma-associated oncogene homolog -1(Gli-1) and Matrix metalloproteinase-2(MMP-2) in gastric cancer.Shh and Gli-1 are the molecules of Hedgehog(Hh) signaling pathway. MMP-2 is the member of matrix metalloproteinase family. Methods The expression of Shh,Gli-1 and MMP-2 proteins was examined by immunohistochemistry in the human gastric cancer tissues and the human gastric polyp and the normal gastric mucosa tissues of 40 cases. Results The positive expression rates of Shh,Gli-1 and MMP-2 in gastric cancer were 62.5%,67.5% and 72.5% respectively, which were significantly higher than those in the gastric polyp tissues (the positive expression rates were 27.5%,37.5% and 32.5% respectively) and normal gastric mucosa tissues (the positive expression rates were 22.5%,17.5% and 12.5% respectively),P<0.05.The expression of Shh,Gli-1 and MMP-2 was not correlated with the sex,age or histological type(P>0.05),but was correlated with depth of invasion,differentiation level and lymphonode metastasis in gastric cancer(P<0.05). The expression of Shh and Gli-1 was positive correlated with MMP-2. Conclusion Hedgehog(Hh)signaling pathway may have great effects on enhancing the invasive ability of gastric cancer by upregulating MMP-2 protein through some unknown mechanisms.The combined detection of the expression level of Shh,Gli-1 and MMP-2 in gastric cancer tissues might be used as an Objective references for assessing the prognosis of gastric cancer.