In this study, gastric cancer progression was correlated with the over-expression of erythropoietin-producing hepatocellular (Eph)A2 receptor and down-expression of epithelial cadherin (E-cadherin). Immunohistochemistry of EphA2 and E-cadherin were performed on these tumor samples from 165 primary lesions of gastric cancer. The results showed that expression of EphA2 was obviously increased in gastric cancer tissues (P<0.01), which was positively correlated with the depth of cancer invasion, tumor-node-metastasis (TNM) stage and lymph node metastasis (P<0.05). Meanwhile, the expression of E-cadherin was significantly reduced (P<0.01), which was negatively correlated with the depth of cancer invasion, grade of tumor differentiation, TNM stage and lymph node metas tasis (P<0.05). The correlation between EphA2 and E-cadherin expression was negative (r=-0.198, P=0.011). In conclusion, either the over-expression of EphA2 or the down-expression of E-cadherin is correlated with cancer progression and lymphogenous metastasis in gastric cancer, suggesting that both of them may play an important role in tumor progression and metastasis.