Genetic polymorphisms of genes whose products are responsible for activities, such as xenobiotic metabolism, mutagen detoxification and DNA-repair, have been predicted to be associated with the risk of developing lung cancer (LC). The association of LC with tobacco smoking has been extensively investigated, but no studies have focused on the Arab ethnic- ity. Previously, we examined the association between genetic polymorphisms among Phase I and Phase II metabolism genes and the risk of LC. Here, we extend the data by examining the correlation of OGG1 Ser326Cys combined with CYP1A1 (Ile462Val and MspI) and GSTP1 (Ile105Val and Ala103Val) polymorphisms with the risk of LC. Polymerase chain reaction- restriction fragment length polymorphism (PCR–RFLP) and gene sequencing were carried out for genotyping the OGG1 polymorphisms of 123 LC patients and 129 controls. No significant differences in the frequencies of the OGG1 mutant allele between patients and controls were found. The distributions of heterozygous Ser/Cys or Cys/Cys genotypes of OGG1 were not associated with the risk of LC either according to the histological types of LC or based on waterpipe tobacco (WP) smoking status. In contrast, the combined effect of OGG1 variants with CYP1A1 and GSTP1 variants revealed a significant correlation with the OGG1 Ser326Cys—CYP1A1 MspI variants pairing. This association was significant (p=0.001) in individuals who carried homozygous or heterozygous variant type genotypes of both genes in a reference with carriers of both wild-type genotypes (wt/wt − wt/wt). The odds ratios were 2.99 (95% CI 1.67–5.36), 2.68 (95% CI 1.08–6.62), and 2.80 (95% CI 1.18–6.69) for those who carried (wt/wt − wt/vt + vt/vt), (wt/vt + vt/vt − wt/wt), and (wt/vt + vt/vt − wt/vt + vt/ vt), respectively. The study suggests a limited correlation is present between carrying OGG1 Ser326Cys polymorphism and the risk of developing LC in Arab populations.