Introduction: Nicotine serves as the primary addictive component of tobacco. While it is not a carcinogen itself, it plays an important role in encouraging smoking and ongoing exposure to numerous carcinogenic substances found in tobacco. The half-life of nicotine tends to be extended in individuals with reduced P450 2A6 activity, and smokers with lower enzyme activity frequently reduce either the intensity of their smoking or the number of cigarettes they consume when compared to individuals with 'normal' enzyme activity. Hence, a study assessed CYP2A6 polymorphisms and quit attempts among smokers. Materials and methods: 5ml of salivary samples were collected from 100 smokers and 100 nonsmokers who had visited Saveetha Dental College in April- May 2023. DNA isolation was done, followed by PCR analysis and Amplification with RFLP. Quit attempts, duration of quit attempts, and methods employed for smoking abstention were assessed using a questionnaire. The statistical association between quit attempts and CYP2A6 (rs56113850) polymorphism was done using the Chi-square test. Results: About 27.9% of smokers had an attempt to quit smoking previously; the rest of smokers (72.1%) did not make an attempt to quit the habit. About 74% smokers have the normal allele (T), the rest 26% have a variant allele (C), about 73% of non-smokers have a normal allele, and the rest 27% have a variant allele. Association between CYP2A6 allele variants and interest to quit scale showed that the normal genotype has a higher scale of interest in quitting tobacco, and the homozygous variant genotype shows the least interest towards quitting tobacco usage, suggesting that there is an association between gene polymorphism and quit attempts. Conclusion: In the present study, there is an association between quit attempts and CYP2A6 polymorphisms among the smokers who had visited the dental hospital. However, the association is not statistically significant.