Endocan overexpression has been reported to be associated with poor prognosis in various cancer types such as breast cancer, kidney cancer, and lung cancer. However, the biological and prognostic significance of endocan in gastric cancer remains unknown. Here, we investigated the expression status of endocan in gastric cancer. Endocan expression status was determined in 255 gastric cancer specimens by immunohistochemical staining. The association of endocan protein with clinicopathological parameters and prognosis was subsequently determined. The oncogenic role of endocan in gastric cancer was examined using a small interfering RNA (siRNA) approach. Spearman regression correlation analysis showed that endocan expression was associated with the pathological tumor stage. In Cox regression analysis, endocan expression was found to be an independent prognostic factor for survival. Endocan promoted gastric cancer cell proliferation. Our findings indicate that endocan is a potential target for therapeutic intervention in gastric cancer.