PURPOSE This study aimed to examine the quality of life of tobacco farmers and their desire to stop growing tobacco. METHODS A cross-sectional home-based survey was conducted between October 2021 and January 2022 among 2,970 Virginia and Burley tobacco farmers in Northern Thailand. Multivariate logistic regression models were used to determine the association between farmers' characteristics and their quality of life and a desire to stop planting tobacco. RESULTS In total, 58.5% of the participants wanted to stop growing tobacco, and most had a lower quality of life than the mean. Nine independent variables were associated with a desire to stop tobacco farming: having a low level of economic quality of life (adjusted odds ratio [ORAdj], 5.42; 95% CI, 3.8 to 7.8); having a high environmental quality of life (ORAdj, 4.60; 95% CI, 3.3 to 6.5); belonging to the Tobacco Farmers' Association (ORAdj, 3.04; 95% CI, 2.1 to 4.5); growing tobacco on their own land (ORAdj, 2.12; 95% CI, 1.8 to 2.6); having a low social quality of life (ORAdj, 1.69; 95% CI, 1.4 to 2.1); having a low health quality of life (ORAdj, 1.69; 95% CI, 1.4 to 2.1); having a low spiritual quality of life (ORAdj, 1.41; 95% CI, 1.2 to 1.7); being Burley tobacco farmers (ORAdj, 1.33; 95% CI, 1.0 to 1.8); and having a low family quality of life (ORAdj, 0.49; 95% CI, 0.4 to 0.6). CONCLUSION The majority of the tobacco farmers had a declining quality of life, particularly economic and environmental quality of life, resulting in reducing growing tobacco. National and regional support are needed to help these farmers effectively grow alternative crops, and financial support to make such conversions.