As one of the most notorious atmospheric pollutants, NOx not only promotes the formation of ozone but also has adverse health effects on humans. It is therefore of great importance to study the sources of NOx and its effects on human health. The Comprehensive Air Quality Model (CAMx) modeling system and ozone source apportionment technology (OSAT) were used to study the contribution of NOx from different emission sources over southern China. The results indicate that heavy duty diesel vehicles (HDDVs) and industrial point sources are the two major local NOx sources, accounting for 30.8% and 18.5% of local NOx sources, respectively. In Hong Kong, marine emissions contributed around 43.4% of local NOx in 2011. Regional transport is another important source of this pollutant, especially in February and November, and it can contribute over 30% of ambient NOx on average. Power plant point emission is an significant regional source in Zhuhai, Zhongshan and Foshan. The total emission sources are estimated to cause 2119 (0–4405) respiratory deaths and 991 (0–2281) lung cancer deaths due to long-term exposure to NOx in the Pearl River Delta region. Our results suggest that local governments should combine their efforts and vigorously promote further reduction of NOx emissions, especially for those sources that make a substantial contribution to NOx emissions and affect human health: HDDV, LDGV, industrial point sources and marine sources.