Hand, foot and mouth disease (HFMD) has recently been recognized as a critical challenge to disease control and public health response in China. This study aimed to quantify the association between temperature and HFMD in Chengdu. Daily HFMD cases and meteorological variables in Chengdu between January 2010 and December 2013 were obtained to construct the time series. A distributed lag non-linear model was performed to investigate the temporal lagged association of daily temperature with age- and gender-specific HFMD. A total of 76,403 HFMD cases aged 0-14 years were reported in Chengdu during the study period, and a bimodal seasonal pattern was observed. The temperature-HFMD relationships were non-linear in all age and gender groups, with the first peak at 14.0-14.1 °C and the second peak at 23.1-23.2 °C. The high temperatures had acute and short-term effects and declined quickly over time, while the effects in low temperature ranges were persistent over longer lag periods. Males and children aged <1 year were more vulnerable to temperature variations. Temperature played an important role in HFMD incidence with non-linear and delayed effects. The success of HFMD intervention strategies could benefit from giving more consideration to local climatic conditions.