【Abstract】Objective To explore the expression of glycogen synthase kinase3 (GSK3β) in gastroenteropancreatic neuroendocrine neoplasms (GEPNENs) and its relationship with clinicopathological characteristics and prognosis. Methods 69 patients diagnosed as GEPNENs from January, 2010 to December, 2017 were selected from the First Affiliate Hospital of Xi’an Jiaotong University for this study. 69 GEPNENs’ tissues were collected and the expression level of GSK3β was evaluated by immunohistochemistry, with 10 normal tissues served as control. A statistical analysis was performed by using SPSS 21.0. The relationship between clinicopathological characteristics and patients’ survival were investigated by KM survival analysis and Cox regression analysis. Results GSK3β was significantly igher expressed in the 69 tumor tissues tested than that of in control group (P=0006). The expression of GSK3β in patients with stage Ⅲ+Ⅳ was higher than that of stage Ⅰ+Ⅱ (P=0020); the expression level of GSK3β in patients with G1+G2 was lower than that of G3 (P=0001). The expression level of GSK3β in patients without lymphatic metastasis was also lower than that of those with lymphatic metastasis (P=0022). For 69 patients with GEPNENs, overall survival was 66.7%. Median overall survival was 45 months. For survival analysis, the patients’ survival distribution with weakpositive and positive expression of GSK3β (37 cases, 536%, unreached) was better than those with strongpositive expression of GSK3β (32 case, 464%, 247 month) (P=0013). Among the patients of weakpositive and positive expression of GSK3β, only those with G1 + G2 (27 cases, 73%, unreached) showed superior survival than those with G3 (10 cases, 27%, 35 months) (P=0.004). Conclusion The overexpression of GSK3β in GEPNENs tumor tissues indicated poor survival. Grade could predict prognosis in the patients of weakpositive and positive GSK3β expression.