Air pollution, a major environmental and health challenge in metropolitan areas, affects quality of life and causes serious health issues. This study aimed to examine daily trends of selected air quality indices (AQI, AQHI, AQRI, and CAQI) and their relationship with trends of daily mortality in Tabriz megacity from March 21, 2021 to March 20, 2023. It used data from the East Azerbaijan Provincial Environmental Protection Agency on air pollutants (CO, SO, NO, O, PM, PM) and meteorological data (temperature & pressure) from the East Azerbaijan Provincial Meteorological Organization. Daily mortality (including total, infectious, respiratory, and cardiovascular deaths) was obtained from the Health and Treatment Deputy of East Azerbaijan. Following WHO data validation standards, the selected air quality indices were calculated and compared with daily mortality trends. Results showed that in 2021, Tabriz air quality was generally good, but in 2022, the number of days with "unhealthy" air quality, increased obviously. The Air Quality Health index (AQHI) showed a stronger correlation (p < 0.01) with daily mortality than other indices, suggesting greater accuracy in reflecting public health impacts. Moreover, on unhealthy or very unhealthy air days, daily mortality significantly increased. These findings highlight the value of multivariate indices like AQHI in monitoring pollution's health effects and guiding policymakers and urban managers to mitigate impacts. Our country currently uses AQI, which identifies only one main pollutant and cannot reflect combined health effects of multiple pollutants. This study recommends replacing AQI with AQHI for a more accurate assessment of health risks.