Background: This study was carried out to investigate the interaction of p53 codon 72 polymorphism, dietary and tobacco habits with reference to risk of stomach cancer in Mizoram, India. A total of 105 histologically confirmed stomach cancer cases and 210 age, sex and ethnicity matched healthy population controls were included in this study. Materials and Methods: The p53 codon 72 polymorphism was detected by PCR-RFLP and sequencing. H. pylori infection status was determined by ELISA. Information on various dietary and tobacco related habits was recorded with a standard questionnaire. Results: This study revealed that overall, the Pro/Pro genotype was significantly associated with a higher risk of stomach cancer (OR, 2.54; 95%CI, 1.01-6.40) as compared to the Arg/Arg genotype. In gender stratified analysis, the Pro/Pro genotype showed higher risk (OR, 7.50; 95%CI, 1.20-47.0) than the Arg/Arg genotype among females. Similarly, the Pro/Pro genotype demonstrated higher risk of stomach cancer (OR, 6.30; 95%CI, 1.41-28.2) among older people (>60 years). However, no such associations were observed in males and in individuals <60 years of age. Smoke dried fish and preserved meat (smoke dried/sun dried) consumers were at increased risk of stomach cancer (OR, 4.85; 95%CI, 1.91-12.3 and OR, 4.22; 95%CI, 1.46-12.2 respectively) as compared to non-consumers. Significant gene-environment interactions exist in terms of p53 codon 72 polymorphism and stomach cancer in Mizoram. Tobacco smokers with Pro/Pro and Arg/Pro genotypes were at higher risk of stomach cancer (OR, 16.2; 95%CI, 1.72-153.4 and OR, 9.45; 95%CI, 1.09-81.7 respectively) than the non-smokers Arg/Arg genotype carriers. The combination of tuibur user and Arg/Pro genotype also demonstrated an elevated risk association (OR, 4.76; 95%CI, 1.40-16.21). Conclusions: In conclusion, this study revealed that p53 codon 72 polymorphism and dietary and tobacco habit interactions influence stomach cancer development in Mizoram, India.