Long non-coding RNAs (lncRNAs) have been proposed as promising diagnostic and prognostic biomarkers for cancer. We investigated the associations of RNA polymerase II subunit E (POLR2E) rs3787016 polymorphism with the risk and prognosis of gastric cancer (GC). The study subjects included 368 GC patients who underwent surgical resection and 294 healthy volunteers, adjusted for age, gender, smoking status, alcohol status, and Helicobacter pylori infection status. The data was subjected to logistic regression analyses and revealed that the subjects carrying AA genotype of rs3787016 in POLR2E had a significant 1.85-1.98-fold increased risk of GC when compared with those carrying GG genotype (adjusted OR=1.979, 95% CI=1.198-3.267; p=0.008) or those carrying AG/GG genotypes (adjusted OR=1.847, 95% CI=1.222-2.793; p=0.004). For the GC patients, the AA genotype of rs3787016 was significantly correlated with poorly differentiated GC (p=0.018), advanced TNM stage (p=0.023), higher depth of invasion (p=0.022), positive lymph node metastasis (p=0.01), and worse overall survival (OS; p=0.004). Multivariate analysis confirmed that the POLR2E rs3787016 polymorphism is an independent prognostic factor for GC (HR=1.668, 95% CI=1.058-2.631; p=0.028). Our cumulative results thus suggest that the presence of POLR2E rs3787016 polymorphism could serve as a genetic factor that affects the susceptibility to and the prognosis of GC.