Exposure to second-hand smoke (SHS) is prevalent in many countries, but the problem’s scope is poorly understood globally, especially in developing countries. We aimed to estimate SHS exposure and its national and subnational burden of diseases in Iran, the second-largest country in the Middle East, during 2009–2020. The burden of diseases from SHS was estimated as disability-adjusted life years (DALYs) for adolescents (10–18) year’s non-smokers. Using comparative risk assessment methodologies, the calculations were based on disease-specific relative risk estimates with national and subnational SHS exposure data, and the uncertainty and sensitivity analysis was performed. The results of study showed that the trend of exposure to SHS is increasing in Iran. The highest DALY was related to lower respiratory infection (LRI), asthma, and otitis media, respectively. The national average asthma burden (DALY/100,000) has increased from 17.4 (11.8_23.9) in 2009 to 21.3 (13.9_30) in 2020, LRI decreased from 25.8 (21.5_30.2) to 19.8 (16.7_23.1), and national average burden of otitis media (DALY/100,000) has increased from 3.1(1.9_4.6) to 3.9(2.4_5.6). The increasing trend of otitis media and asthma DALYs attributable to SHS exposure in Iran requires more attention from policymakers to protect the population.