ObjectivesTo assess the prevalence of dry eye disease (DED) in the Uyghur population in Hotan, Xinjiang, and to identify risk factors associated with this disorder.MethodsBetween January and September of 2020, 5,121 Uyghur subjects aged 18 − 98 years from 105 villages were selected and studied cross-sectionally using a whole-group random sampling method in the Hotan area, Xinjiang, China. The Ocular Surface Disease Index questionnaire was used to collect subjective symptoms of DED and examine tear-film break-up times. The break up time and Schirmer’s test were used to collect objective signs, to determine the prevalence of DED and its risk factors.ResultsA total of 5,121 subjects aged 18 − 98 years were recruited from the Uyghur population in the Hotan region of Xinjiang, China, for eye examinations and questionnaire surveys. A total of 40.6% (2,078/5,121) were diagnosed with DED, of which 38.3% were male and 41.9% were female. The prevalence of DED was the highest in subjects ≥ 65 years of age, with 47.8% in males and 53.3% in females. The lowest occurrence was in subjects 18 − 44 years of age, with 32.5% in males and 33.7% in females. Older age, tea drinking, and staying awake late were risk factors affecting the severity of DED prevalence (p< 0.05), but there was no significant difference in sex, presence of diabetes, or presence of hypertension (p> 0.05).ConclusionThe prevalence of DED in the study population was 40.6%, and its prevalence was higher in females, when compared with males. The prevalence of dry eye also increased with age, and at an advanced age, female sex, smoking, staying awake late, and not exercising were risk factors for DED.