Previous studies demonstrated that the El Niño-Southern Oscillation (ENSO) could modulate regional climate thus influencing air quality in the low-middle latitude regions like southern China. However, such influence has not been well evaluated at a long-term historical scale. To filling the gap, this study investigated two-decade (2002 to 2020) aerosol concentration and particle size in southern China during the whole dynamic development of ENSO phases. Results suggest strong positive correlations between aerosol optical depth (AOD) and ENSO phases, as low AOD occurred during El Niño while high AOD occurred during La Niña event. Such correlations are mainly attributed to the variation of atmospheric circulation and precipitation during corresponding ENSO phase. Analysis of the angstrom exponent (AE) anomalies further confirmed the circulation pattern, as negative AE anomalies is pronounced in El Nino indicating the enhanced transport of sea salt aerosols from the South China Sea, while the La Niña event exhibits positive AE anomalies which can be attributed to the enhanced import of northern fine anthropogenic aerosols. This study further quantified the AOD variation attributed to changes in ENSO phases and anthropogenic emissions. Results suggest that the long-term AOD variation from 2002 to 2020 in southern China is mostly driven (by 64.2%) by the change of anthropogenic emissions from 2002 to 2020. However, the ENSO presents dominant influence (70.5%) on year-to-year variations of AOD during 2002–2020, implying the importance of ENSO on varying aerosol concentration in a short-term period.