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In the past two decades, epidemiological studies have shown that air pollution is one of the causes of morbidity and mortality. In this study the effect of PM10, PM2.5, NO2, SO2 and O3 pollutants on human health among the inhabitants of Mashhad has been evaluated. To evaluate the health effects due to air pollution, the AirQ model software 3.3.2, developed by WHO European Centre for Environment and Health, was used. The daily data related to the pollutants listed above has been used for the short term health effects (total mortality, cardiovascular and respiratory mortality, hospitalization due to cardiovascular and respiratory diseases, chronic obstructive pulmonary disease and acute myocardial infarction). PM2.5 had the most health effects on Mashhad inhabitants. With increasing in each 10 μg/m3, relative risk rate of pollutant concentration for total mortality due to PM10, PM2.5, SO2, NO2 and O3 was increased of 0.6%, 1.5%, 0.4%, 0.3% and 0.46% respectively and, the attributable proportion of total mortality attributed to these pollutants was respectively equal to 4.24%, 4.57%, 0.99%, 2.21%, 2.08%, and 1.61% (CI 95%) of the total mortality (correct for the non-accident) occurred in the year of study. The results of this study have a good compatibly with other studies conducted on the effects of air pollution on humans. The AirQ software model can be used in decision-makings as a useful and easy tool.We assessed the air pollution impact on mortality in Mashad, Iran in 2014–2015.The methodology developed by the WHO was used for this purpose.The effect of PM10, PM2.5, NO2, SO2 and O3 on human health has been evaluated.PM2.5 had the most health effects on Mashhad inhabitants.