Drug metabolizing genes are involved in the detoxification of chemical carcinogens. Polymorphisms in drug-metabolizing genes affect the risk of some forms of cancer. We analyzed six polymorphisms to evaluate their association with risk for non-Hodgkin lymphoma (NHL), and to examine whether smoking modifies these associations in population-based study in Korea (713 cases and 1,700 controls). The GSTP1 rs1695 AG and the combined AG/GG genotypes were associated with decreased risk of NHL (odds ratio (OR)AG = 0.67, 95% confidence interval (CI) = 0.55–0.82; ORAG/GG = 0.66, 95% CI = 0.54–0.80) and DLBCL (ORAG = 0.63, 95% CI = 0.49–0.82; ORAG/GG = 0.64, 95% CI = 0.50–0.82). For T-cell lymphoma, only the combined AG/GG genotype was associated with decreased risk (ORAG/GG = 0.65, 95% CI = 0.44–0.96). The CYP1A1 rs1048943 AG genotype and the combined AG/GG genotypes were associated with increased risk of NHL (ORAG = 1.28, 95% CI = 1.07–1.54; ORAG/GG = 1.26, 95% CI = 1.06–1.51) and DLBCL (ORAG = 1.32, 95% CI = 1.04–1.66; ORAG/GG = 1.30, 95% CI = 1.03–1.63), but not T-cell lymphoma. Smoking does not modify the association between these polymorphisms and NHL risk. Our data provide evidence that the GSTP1 rs1695 and the CYP1A1 rs1048943 genotypes affect the risk of NHL in Korea. Am. J. Hematol. 2009. © 2009 Wiley-Liss, Inc.