BackgroundHand, foot, and mouth disease (HFMD) is a significant public health issue in China, and numerous studies have indicated a close association between HFMD incidence and meteorological factors. This study aims to investigate the relationship between meteorological factors and HFMD in Yangzhou City, Jiangsu Province, China.MethodsHFMD case reports and meteorological data from Yangzhou City between 2017 and 2022 were extracted from the National Notifiable Infectious Disease Surveillance System and the Meteorological Data Sharing Service System, respectively. A generalized additive model (GAM) was employed to assess the exposure-response relationship between meteorological factors and HFMD. Subsequently, a distributed lag nonlinear model (DLNM) was used to explore the exposure-lag-effect of meteorological factors on HFMD.ResultsHFMD in Yangzhou City exhibits obvious seasonality and periodicity. There is an inverted “U” shaped relationship between average temperature and the risk of HFMD, with the maximum lag effect observed at a temperature of 25°C with lag 0 day (RR = 2.07, 95% CI: 1.74–2.47). As the duration of sunshine and relative humidity increase, the risk of HFMD continuously rises, with the maximum lag effect observed at a sunshine duration of 12.4 h with a lag of 14 days (RR = 2.10, 95% CI: 1.17–3.77), and a relative humidity of 28% with a lag of 14 days (RR = 1.21, 95% CI: 1.01–1.64). There is a “U” shaped relationship between average atmospheric pressure and the risk of HFMD, with the maximum effect observed at an atmospheric pressure of 989 hPa with no lag (RR = 1.45, 95% CI: 1.25–1.69). As precipitation increases, the risk of HFMD decreases, with the maximum effect observed at a precipitation of 151 mm with a lag of 14 days (RR = 1.45, 95% CI: 1.19–2.53).ConclusionMeteorological factors including average temperature, average atmospheric pressure, relative humidity, precipitation, and sunshine duration significantly influenced the risk of HFMD in Yangzhou City. Effective prevention measures for HFMD should be implemented, taking into account the local climate conditions.