Lung cancer remains the most common cancer in the world. The genetic polymorphisms (rs2853669 in TERT, rs1052133 in OGG1, and rs16969968 in CHRNA5 genes) were shown to be strongly associated with the risk of lung cancer. Our study's aim is to elucidate whether these polymorphisms predispose Eastern Algerian population to non-small-cell lung cancer (NSCLC). To date, no study has considered this association in the Algerian population. This study included 211 healthy individuals and 144 NSCLC cases. Genotyping was performed using TaqMan probes and Sanger sequencing, and the data were analyzed using multivariate logistic regression adjusted for covariates. The minor allele frequencies (MAFs) of TERT rs2853669, CHRNA5 rs16969968, and OGG1 rs1052133 polymorphisms in controls were C: 20%, A: 31%, and G: 29%, respectively. Of the three polymorphisms, none shows a significant association, but stratified analysis rs16969968 showed that persons carrying the AA genotype are significantly associated with adenocarcinoma risk (pAdj = 0:03, ORAdj = 2:55).Smokers with an AA allele have a larger risk of lung cancer than smokers with GG or GA genotype (pAdj = 0:03, ORAdj = 3:91), which is not the case of nonsmokers. Our study suggests that CHRNA5 rs16969968 polymorphism is associated with a significant increase of lung adenocarcinoma risk and with a nicotinic addiction.