The validity of using the Air Pollution Index (API) to assess health impacts of air pollution and potential modification by individual characteristics on air pollution effects remain uncertain. We applied distributed lag non-linear models (DLNMs) to assess associations of daily API, specific pollution indices for PM10, SO2, NO2 and the weighted combined API (APIw) with mortality during 2003–2011 in Guangzhou, China. An increase of 10 in API was associated with a 0.88% (95% confidence interval (CI): 0.50, 1.27%) increase of non-accidental mortality at lag 0–2 days. Harvesting effects appeared after 2 days’ exposure. The effect estimate of API over lag 0–15 days was statistically significant and similar with those of pollutant-specific indices and APIw. Stronger associations between API and mortality were observed in the elderly, females and residents with low educational attainment. In conclusion, the API can be used to communicate health risks of air pollution.