Background: A very high incidence of lung cancer is observed in Mizoram and Manipur, North East India.We conducted a population based case control study to establish associations of p53 codon 72 polymorphisms andinteractions with environmental factors for this high incidence. Material and Methods: A total of 272 lung cancercases and 544 controls matched for age (±5 years), sex and ethnicity were collected and p53 codon 72 polymorphismgenotypes were analyzed using a polymerase chain based restriction fragment length polymorphism assay. Weused conditional multiple logistic regression analysis to calculate adjusted odds ratios and 95% confidenceintervals after adjusting for confounding factors. Results: p53 Pro/Pro genotype was significantly associated withincreased risk of lung cancer in the study population (adjusted OR=2.14, CI=1.35-3.38, p=0.001). Interactionsof the p53 Pro/Pro genotype with exposure to wood smoke (adjusted OR=3.60, CI=1.85-6.98, p<0.001) andcooking oil fumes (adjusted OR=3.27, CI=1.55-6.87, p=0.002), betel quid chewing (adjusted OR=3.85, CI=1.96-7.55, p<0.001), tobacco smoking (adjusted OR=4.42, CI=2.27-8.63, p<0.001) and alcohol consumption (adjustedOR=3.31, CI=1.10-10.03, p=0.034) were significant regarding the increased risk of lung cancer in the studypopulation. Conclusions: The present study provided preliminary evidence that a p53 codon 72 polymorphismmay effect lung cancer risk in the study population, interacting synergistically with environmental factors.