Sulfotransferases (SULTs) are very important multifunctional enzymes that catalyze sulfonate conjugation, which is an important pathway in the phase II metabolism of numerous endogenous and exogenous compounds. Sulfotransferase 1A1 (SULT1A1) is active toward a wide range of substrates, including environmental and tobacco carcinogens. This case-control study involved collection of peripheral blood samples (2-5 mL) of 103 lung cancer patients and 122 controls from North Indian subjects. The SULT1A1 polymorphism was determined by using a polymerase chain reaction-restriction fragment length polymorphism method. The association between polymorphisms in the SULT1A1 gene with the risk of lung cancer was estimated by computing odds ratios (OR) and 95% confidence intervals (95% CI), using a multivariate logistic regression analysis. We observed marginally increased risk for mutant genotype (AA) of SULT1A1 for lung cancer (OR = 1.4, 95% CI = 0.48-4.06). A statistically significant association was found for smokers between either of two SULT1A1 genotypes, GA (OR = 10.3, 95% CI = 3.48-31.78, P = 0.000002) or AA (OR = 3.9, 95% CI = 1.99-7.81, P = 0.0002), and lung cancer. The present study indicates that the SULT1A1 genotype may play an important role in the risk of developing lung cancer, especially in cigarette smokers.