Hand, foot, and mouth disease (HFMD) is a common childhood infection that causes a substantial disease burden in the Asia-Pacific region. Various climate variables, such as humidity and temperature, have been associated with HFMD. However, few studies have assessed the impact of PM10 on childhood HFMD. This study investigated the association between PM10 and HFMD. We fitted a standard distributed lag non-linear model to investigate the temporal lagged relationship between PM10 and HFMD, and then further assessed whether this relationship varied by gender and pathogen. Between 2011 and 2015, a total of 122,564 HFMD cases under 15 years of age were reported in Chengdu. The PM10-HFMD associations were shown to be non-linear in all subgroups, with the peak at 101-218 μg/m3. Male children were more sensitive to PM10 effects. For pathogen-specific relative risks, we found that the risk estimates were generally higher in cases of CVA16 infection. Our study provides evidence that PM10 increases the risk of HFMD. Authorities and parents should be fully aware of the impact of PM10 on childhood HFMD. Furthermore, appropriate protective measures should be taken to reduce risks.