Background: Association of angiotensin converting enzyme (ACE) gene polymorphisms with lung cancersusceptibility remains uncertain and varies with ethnicity. Northeast India represents a geographically, culturally,and ethnically isolated population. The area reports an especially high rate of tobacco usage in a variety ofways of consumption, compared with the rest of the Indian population. Materials and Methods: We conducteda population based case control study in two major high risk region for lung cancer from Northeast India. Atotal of 151 consecutive lung cancer cases diagnosed histopathologically and equal numbers of controls wererecruited with record of relevant sociodemographic information. Blood samples were collected and processedto identify ACE gene polymorphism. Results: Significantly higher (40.4 % vs 29.1%, OR=1.97, CI=1.04-3.72;p=0.037) prevalence of the ACE II genotype was observed among lung cancer cases. Smoking was significantlyassociated with increased risk of lung cancer (OR=1.70, CI=1.02-2.81; p=0.041). An enhanced risk was alsoobserved for interaction of ACE II genotype with tobacco smoking (OR=4.09, CI=1.51-11.05; p=0.005) andchewing (OR=3.68, CI=1.22-11.13; p=0.021). Conclusions: The present study indicates significant association sof the ACE II genotype with lung cancer in high risk Northeast India.