In recent years, hand, foot, and mouth disease (HFMD) has been increasingly recognized as a critical challenge to disease control and prevention in China. Previous studies have found that meteorological factors such as mean temperature and relative humidity were associated with HFMD. However, little is known about whether the diurnal temperature range (DTR) has any impact on HFMD. This study aimed to quantify the impact of DTR on childhood HFMD in 18 cities in Sichuan Province. A distributed lag non-linear model was adopted to explore the temporal lagged association of daily temperature with age-, gender- and pathogen-specific HFMD. A total of 290 123 HFMD cases aged 0–14 years were reported in the 18 cities in Sichuan Province. The DTR–HFMD relationships were non-linear in all subgroups. Children aged 6–14 years and male children were more vulnerable to the temperature changes. Large DTR had the higher risk estimates of HFMD incidence in cases of EV71 infection, while small DTR had the higher risk estimates of HFMD incidence in cases of CV-A16 infection. Our study suggested that DTR played an important role in the transmission of HFMD with non-linear and delayed effects.