Objective: To investigate the EphA2 and VEGF-C expressions in gastric cancer and their clinical significance. Methods: The protein expressions of VEGF-C and EphA2 as well as the lymphatic vessel density (LVD) in 82 paired specimens of gastric cancer and adjacent gastric tissue were determined by immunohistochemical staining. The mRNA expressions of EphA2 and VEGF-C in 20 paired specimens of gastric cancer and adjacent gastric tissue were detected by real-time RT-PCR. The relations of EphA2 and VEGF-C expressions with the clinicopathologic characteristics of the patients and lymphangiogenesis were analyzed. Results: The positive expression rates of both EphA2 and VEGF-C in gastric cancer tissue were significantly higher than those in adjacent gastric tissue (65.8% vs. 42.6%; 71.9% vs. 39.0%, both P<0.05). The high expressions of EphA2 and VEGF-C were significantly associated with the depth of tumor invasion, lymph node metastasis and TNM stage (all P<0.001). The LVD count in gastric cancer tissue with high EphA2 or VEGF-C expression was significantly higher than that in gastric cancer tissue with low EphA2 or VEGF-C expression (15.25±5.41 vs. 10.95±5.41, P=0.001; 14.87±5.71 vs. 11.00±5.01, P=0.006). There was a significant correlation between EphA2 and VEGF-C in either protein or mRNA expression in gastric cancer tissue (r=0.375, P=0.001; r=0.559, P=0.01). Conclusion: Both EphA2 and VEGF-C expressions are increased in gastric cancer tissue, and they may jointly promote lymphangiogenesis and lymph node metastasis in gastric cancer.