Objective: To investigate the expression and clinical significance of interleukin (IL)-5 in gastric cardia cancer. Methods: Forty-three eases of gastric cardia cancer tissue and corresponding paracancerous tissues were collected, and the expression of IL-5 in specimen above were detected by immunohistochemical analysis. The relationship between expression of IL-5 and clinicopathological features and prognosis of patients with gastric cardia cancer was analyzed. Results: Compared with adjacent mucous membrane tissues, the expression of IL-5 were significantly increased in tissues of gastric cardia cancer (positive expression rate was 74.4% vs 37.2%, P<0.05). The expression of IL-5 in gastric cardia cancer tissues was related with tumor TNM staging (P=0.029), differentiation degree (P=0.011) and lymph node metastasis (P=0.020), which was not related with gender (P=0.755), age (P=0.795), tumor diameter (P=0.133), distant metastasis (P=0.545), smoking history (P=0.133), and drinking history (P=0.545). Cox proportional hazard regression analysis showed that IL-5, tumor TNM stage, differentiation degree and lymph node were associated with prognosis. Conclusion: The expression of IL-5 was up-regulated in gastric cardia cancer tissues and may contribute to predict the prognosis of gastric cardia cancer.