Hand, foot, and mouth disease (HFMD) remains a serious health threat to young children. Urumqi is one of the most severely affected cities in northwestern China. This study aims to identify the spatiotemporal distribution characteristics of HFMD, and explore the relationships between driving factors and HFMD in Urumqi, Xinjiang. METHODS: HFMD surveillance data from 2014 to 2018 were obtained from the China Center for Disease Control and Prevention. The center of gravity and geographical detector model were used to analyze the spatiotemporal distribution characteristics of HFMD and identify the association between these characteristics and socioeconomic and meteorological factors. RESULTS: A total of 10,725 HFMD cases were reported in Urumqi during the study period. Spatially, the morbidity number of HFMD differed regionally and the density was higher in urban districts than in rural districts. Overall, the development of HFMD in Urumqi expanded toward the southeast. Temporally, we observed that the risk of HFMD peaked from June to July. Furthermore, socioeconomic and meteorological factors, including population density, road density, GDP, temperature and precipitation were significantly associated with the occurrence of HFMD. CONCLUSIONS: HFMD cases occurred in spatiotemporal clusters. Our findings showed strong associations between HFMD and socioeconomic and meteorological factors. We comprehensively considered the spatiotemporal distribution characteristics and influencing factors of HFMD, and proposed some intervention strategies that may assist in predicting the morbidity number of HFMD.