The study aims to depict the temporal and spatial distributions of hand-foot-and-mouth disease (HFMD) in Xinjiang, China and reveal the relationships between the incidence of HFMD and meteorological factors in Xinjiang. With the national surveillance data of HFMD in Xinjiang and meteorological parameters in the study area from 2008 to 2016, in GeoDetector Model, we examined the effects of meteorological factors on the incidence of HFMD in Xinjiang, China, tested the spatial-temporal heterogeneity of HFMD risk, and explored the temporal-spatial patterns of HFMD through the spatial autocorrelation analysis. From 2008 to 2016, the HFMD distribution showed a distinct seasonal pattern and HFMD cases typically occurred from May to July and peaked in June in Xinjiang. Relative humidity, precipitation, barometric pressure and temperature had the more significant influences on the incidence of HFMD than other meteorological factors with the explanatory power of 0.30, 0.29, 0.29 and 0.21 (P<0.000). The interaction between any two meteorological factors had a nonlinear enhancement effect on the risk of HFMD. The relative risk in Northern Xinjiang was higher than that in Southern Xinjiang. Global spatial autocorrelation analysis results indicated a fluctuating trend over these years: the positive spatial dependency on the incidence of HFMD in 2008, 2010, 2012, 2014 and 2015, the negative spatial autocorrelation in 2009 and a random distribution pattern in 2011, 2013 and 2016. Our findings revealed the correlation between meteorological factors and the incidence of HFMD in Xinjiang. The correlation showed obvious spatiotemporal heterogeneity. The study provides the basis for the government to control HFMD based on meteorological information. The risk of HFMD can be predicted with appropriate meteorological factors for HFMD prevention and control.