Objective/Aim:The aim of this study is to measure the association between oral mucosal lesions (OMLs) and habit of tobacco and alcohol in the population of Guntur city, Andhra Pradesh, South India.Material and Method:A cross-sectional study was conducted on 300 participants in Guntur city with the habit of tobacco and alcohol consumption in various forms who were selected by stratified cluster random sampling technique. Guntur city was divided into four zones, that is, North, East, South, and West; and two administrative wards were randomly selected from each zone as clusters. Information was obtained by interviewing the participant regarding various tobacco-related habits followed by standardized clinical examination in the field. Clinical data were collected using a modified 1980 WHO Pro forma where the basis for diagnosis was established as per the criteria provided by the epidemiology guide for the diagnosis of oral mucosal diseases (WHO). Statistical tests such as Pearson Chi-square were exercised to test the significance, using SPSS version 19.0 with 0.05 as cutoff level of significance.Results:Overall oral soft-tissue lesions were found in 42.4% of the study participants including nicotinic stomatitis, tobacco pouch keratosis, smokers melanosis, mild keratosis of the palate, and chewer's mucosa. In this study, nicotinic stomatitis was found to be the most common soft-tissue lesion among men, while leukoplakia was found to be the most common premalignant lesion with the prevalence being 5.7%. While oral submucous fibrosis was found to be the most common premalignant condition among women. It was found that 13.2% of illiterates (53) were having leukoplakia. In the present study, the lower labial mucosa and buccal mucosa were found to be the most common sites of occurrence of leukoplakia and oral submucous fibrosis.Conclusion:This study gives information on the association of OML in smokers, chewers, alcoholics, and those with mixed habits. This study highlighted six habit-related OML which included potentially malignant disorders such as leukoplakia and oral submucous fibrosis. Future case–control or cohort studies for individual lesions and with larger sample size are necessary to evaluate the risk for OML including potentially malignant conditions and oral cancer resulting from smoking and chewing habits.