The telomere-binding protein TRF2 regulates both telomere protection and telomere length. The fact that TRF2 is up-regulated in some tumors indicates that TRF2 plays a role in cancer. However, the role of TRF2 in gastric cancer has not been fully understood. The aim of this study is to evaluate the expression pattern of TRF2 in gastric cancer and examine the potential mechanism of TRF2 regulation. Our study revealed that the expression of TRF2 analyzed by immunohistochemistry was significantly higher in gastric cancers compared to noncancerous tissues. Moreover, TRF2 methylation was detected in six of 30 (20%) primary gastric cancers and 18 of 30 (60%) paired normal tissues, and the downregulation of TRF2 was strongly correlated with the methylation status (P < 0.001). Our results suggest that hypomethylation might contribute to the upregulation of TRF2 in gastric cancers and this overexpression may play a role in the pathogenesis of gastric cancers.