Aim: To study the effects of curcumin on Helicobacter pylori and N-methyl-N-nitrosourea (MNU)-induced gastric cancer in rats. Materials and Methods: Male Wistar rats were divided into three groups: control (CO), H. pylori inoculation and 30 ppm MNU in drinking water for 20 weeks (Hp + MNU), and H. pylori and MNU supplemented with 60 mg/kg curcumin for 30 weeks (Hp + MNU + Cur). The stomach was removed to examine nuclear factor kappa B (NF-κB) p65, 8-hydroxy-2'-deoxyguanosine (8-OHdG), cyclin D1, and Ki-67 in gastric epithelial cells by immunohistochemistry. The expression of apoptotic cells was measured by terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling reaction and gastric histopathology. Results: Two rats in Hp + MNU developed adenocarcinoma (ADC) of the glandular stomach (40% incidence, n = 5), while in Hp + MNU + Cur, no gastric ADC was found. Histopathology of gastric ADC showed the invasion of malignant cuboidal epithelial cells to submucosal layer. The percentages of NF-κB p65, 8-OHdG, cyclin D1, and Ki-67 immunoreactive cells in Hp + MNU compared with CO were 12.20% ± 1.10% versus 1.86% ± 1.49%, 13.21% ± 0.90% versus 2.84% ± 1.29%, 66.96% ± 5.91% versus 6.06% ± 6.48%, and 42.29% ± 0.08% versus 14.95% ± 0.12%, P < 0.05, respectively. The expression of apoptotic cells significantly increased in Hp + MNU compared with CO (8.41% ± 0.01% vs. 0.53% ± 0.02%, P < 0.05). Curcumin supplementation reduced the gastric cancer incidence compared with Hp + MNU. Percentages of NF-κB p65, 8-OHdG, cyclin D1, and Ki-67 immunoreactive cells in Hp + MNU + Cur compared with Hp + MNU were 4.76% ± 3.73% versus 12.20% ± 1.10%, 1.76% ± 0.94% versus 13.21% ± 0.90%, 24.71% ± 4.62% versus 66.96% ± 5.91%, and 24.99% ± 0.05% versus 42.29% ± 0.08, P < 0.05, respectively. The apoptosis expression was significantly improved (4.14% ± 0.16% vs. 8.41% ± 0.01%, P < 0.05). Conclusion: Curcumin can reduce gastric cancer incidence induced by H. pylori infection and MNU administration through the suppression of key proteins and apoptosis involved in carcinogenesis.