World Health Organization classifies air pollution as the first cause of human cancer. The present study investigated impact of air pollutants on the mortality rates of lung cancer and leukemia in Shiraz, one of the largests cities of Iran. This cross‑sectional (longitudinal) study was carried out in Shiraz. Data on six main pollutants, CO, SO2, O3, NO2, PM10 and PM2.5, were collected from Fars Environmental Protection Agency for 3,001 days starting from 1 January, 2005. Also, measures of climatic factors (temperature, humidity, and air pressure) were obtained from Shiraz Meteorological Organization. Finally, data related to number of deaths due to lung and blood cancers (leukemia) were gathered from Shiraz University Hospital. Relationship between variations of pollutant concentrations and cancers in lung and blood was investigated using statistical software R and MiniTab to perform time series analysis. Results of the present study revealed that the mortality rate of leukemia had a direct significant correlation with concentrations of nitrogen dioxide and carbon monoxide in the air (P<0.05). Therefore, special attention should be paid to sources of these pollutants and we need better management to decrease air pollutant concentrations through, e.g., using clean energy respect to fossil fuels, better management of urban traffic planning, and the improvement of public transport service and car sharing.