Cigarette smoking is a major lifestyle factor leading to different human diseases . The DNA repair gene, thymine DNA glycosylase, is important to cell survival because it stops cells from becoming cancerous protecting/preventing DNA . Exposure to CS may induce genetic changes such as single nucleotide polymorphisms in DNA repair genes . Therefore, the purpose of this study was to investigate the genotype and allele distributions of four TDG SNPs with only smoking behavior in normal patients . Four TDG SNPs-rs4135066 (C/T), rs3751209 (A/G), rs1866074 (C/T), and rs1882018 (C/T) were analyzed by genotyping 235 and 239 blood samples collected from cigarette smokers and non-smokers, among the Saudi population . The results showed that TDG rs4135066 has a significant susceptibility effect observed in long-term smokers (> 5 years; OR = 4.53; P = 0.0347) but not in short-term smokers (≤5 years) in contrast with non-smokers . Also, in smokers aged less than 29 years, the``CT ,"`` TT ,"and``CT + TT"alleles of rs1882018 increased the risk of developing all diseases related to smoking by approximately 6 , 4, and 5 times, respectively, in contrast with the ancestral``CC"homozygous allele . A comparison of the allele distributions of TDG SNPs in a Saudi population with those in other populations represented in the HapMap project showed that the genetic makeup of the Saudi Arabian population appears to differ from that of other ethnicities . Exceptions include the Yoruba people in Ibadan, Nigeria; those of Mexican ancestry in Los Angeles, California; the Luhya population in Webuye, Kenya; Gujarati Indians in Houston, Texas; and the Tuscan population in Italy, which showed similar allelic frequencies for rs3751209 compared to our Saudi population . In this ethnic, we have found a high variation in the distribution of the alleles and genotype frequencies on TDG gene . This variation on TDG SNP's with smoking could lead to increase the susceptibility to many diseases related to smoking habits in this population.