Air pollution contains a complex mixture of poisonous compounds including particulate matter (PM) which has wide spectrum of adverse health effects. The main purpose of this study was to estimate the potential health impacts or benefits due to any changes in annual PM10 level in four major megacities of Iran. The required data of PM10 for AirQ software was collected from air quality monitoring stations in four megacities of Iran. The preprocessing was carried out using macro coding in excel environment. The relationship between different presumptive scenarios and health impacts was determined. We also assessed the health benefits of reducing PM10 to WHO Air Quality Guidelines (WHO-AQGs) and National Ambient Air Quality Standards (NAAQSs) levels with regard to the rate of mortality and morbidity in studied cities. We found that the 10 μg/m3 increase in annual PM10 concentration is responsible for seven (95% CI 6-8) cases increase in total number of deaths per 2 × 105 person. We also found that 10.7, 7.2, 5.7, and 5.3% of total death is attributable to short-term exposure to air pollution for Ahvaz, Isfahan, Shiraz, and Tehran, respectively. We found that by attaining the WHO's proposed value for PM10, the potential health benefits of 89, 84, 79, and 78% were obtained in Ahvaz, Isfahan, Shiraz, and Tehran, respectively. The results also indicated that 27, 10, 3, and 1% of health impacts were attributed to dust storm days for Ahvaz, Isfahan, Shiraz, and Tehran, respectively.