Abstract: Based on the weekly reported data of hand, foot and mouth disease (HFMD) incidence in Wenzhou from 2014 to 2017 and air quality data in the same period, a generalized additive model was established to study the short-term effects of air pollution on the weekly reported number of incidence. The results showed that the four air pollutants SO₂, CO, NO₂ and O₃ had significant and lagging effects on the weekly number of HFMD incidence, and the lagging period was one week. Single pollutant model showed that SO₂, CO and NO₂ were risk factors for HFMD incidence, and the weekly number of HFMD incidence would increase by 2.8%, 43.8% and 0.9% with the increase of average weekly concentration of every 1 μg/m³ SO₂, 1 mg/m³ CO, 1 μg/m³ NO₂ after one week delay, while the weekly number of HFMD incidence would decrease by 0.4% with the increase of average weekly concentration of O₃ at every 1 μg/m³ after one week delay. In the 11 multi-pollutant models composed of SO₂, CO, NO₂ and O₃, the SO₂+CO model was selected as the optimal model according to the QAIC minimum principle. Our results will provide a scientific basis for the prevention and control of HFMD.