Objective Detected Her-2/neu, matrix metalloproteinases-2 (MMP-2) and Leptin in stomach cancer serum and tissue, discussed their roles in occurance and development of gastric cancer. Methods Detected the ex-pression of Her-2/neu, MMP-2 and Leptin in serum by ELISA, and detected the expression of Her-2/neu, MMP-2 and Leptin in stomach cancer tissue by IHC. Results The positive rates of Her-2/neu, MMP-2, Leptin in gas-tric cancer serum were higher than the positive rates in control group ( P<0.05 ) . The positive rates of Her-2/neu, MMP-2, Leptin in gastric cancer tissues were higher than the positive rates in adjacent tissues (P<0.05 ). The positive expressions of two tests had consistency. In tissues, the positive expression rates of Her-2/neu,MMP-2 and Leptin were correlated with the depth of invasion,lymph node metastasis, clinical stage(P<0.05). Their ex-pression was not correlated with sex, age, size, site of tumor and the degree of differentiation. In serum, the posi-tive expression of Her-2/neu was correlated with the depth of invasion, lymph node metastasis, clinical stage( P<0.05 ) . The positive expression of MMP-2 was correlated with lymph node metastasis ( P<0.05 ) . The positive ex-pression of Leptin had no significant correlation with pathological features. Conclusion Her-2/neu,MMP-2 and Leptin promote the occurrence, development and transfer process of gastric cancer. It can be used for clinical diag-nosis, guide the targeted therapy and provide scientific and reasonable reference for gastric cancer prognosis.