Biological behavior, pathological characteristics and prognostic factors of 355 cases with gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) were analyzed in this retrospective study. In our study, 355 patients pathologically diagnosed as GEP-NENs were identified from April 2006 to November 2017 in the Fourth Hospital of Hebei Medical University. The biological behavior, pathological characteristics and prognosis were analyzed retrospectively. There were 355 patients (228 males and 127 females) with a mean age of 58.3±10.7 years. GEP-NENs were detected most frequently in the stomach (48.2%), followed by the pancreas (16.1%), colorectum (14.1%), esophagus (7.6%), duodenum/jejunum(5.6%), liver (4.2%), appendix (2.3%) and gallbladder/bile duct (2.0%). The main clinical manifestations of non-functional GEP-NENs were abdominal pain (88/350, 25.14%), ventosity (77/350, 22.00%) and dysphagia (68/350, 19.43%), which were generally lacking specificity at the first diagnosis. 295 patients were treated surgically, including 45 cases of endoscopic resection and 250 cases of laparoscopic operation. Concerning to pathological grading, there were 22.5% (80/355) patients in grade 1 (G1), 12.7% (45/355) in grade 2 (G2), and 58.9% (209/355) in grade 3 (G3). The median follow-up time was 34 months. Furthermore, the 1-, 3- and 5-year overall survival calculated by Kaplan-Meier method were 80.1%, 59.8%, and 57.5%, respectively. Univariate analysis revealed that tumor site, treatment, operation type, depth of tumor invasion, TNM staging, pathological grading, vascular embolus, lymph node metastasis, tumor size, preoperative leukomonocyte level and preoperative plasma albumin were associated with overall survival (all <0.05). Multivariate analysis showed that treatment, operation type, depth of tumor invasion, TNM staging, pathological grading, vascular embolus, lymph node metastasis and tumor size were independent prognostic factors for GEP-NENs (all <0.05). The clinicopathological characteristics of GEP-NENs should be mastered by clinicians, and the standard treatment measures were also needed to be formulated based on the prognostic factors in order to improve the prognosis of patients.