<p>Kashin–Beck disease (KBD) is an endemic disease characterized by its complex etiology and severe impact on human health. It is also regarded as one of the most serious endemic disease in China. This study aimed to investigate the spatial correlation and determinants of this disease. Monitoring data of children and possible influencing factors were collected from 37 KBD regions in Gansu Province. The spatial autocorrelation method was used to describe the spatial aggregation of KBD, and the spatial regression analysis was used to explore the natural environment and socioeconomic factors influencing KBD incidence. The results showed that the X-ray detection rate of KBD demonstrated a significant negative spatial correlation, with Kangle county and its neighboring areas located in southcenter of Gansu Province were hot spots of KBD. The spatial lag model revealed that rainfall, the proportion of afforestation in cultivated land, and population density had negative effects on the X-ray detection rate of KBD. The prevalence of KBD in Gansu Province is determined by a combination of natural environment and socioeconomic factors. Precision prevention and control should be implemented by the specific conditions of each diseased region.</p>