Objective To investigate the prevalence and risk factors of thyroid nodules in physical examination population of Hotan County People's Hospital, so as to provide a basis for the prevention and treatment of thyroid diseases. Methods A retrospective analysis was conducted on the data of population over 18 years old who underwent physical examination in the Health Examination Center of Hotan County People's Hospital from May 2016 to Jan. 2018. All enrolled subjects underwent thyroid ultrasonography and had complete ultrasonographic information. The subjects were divided into thyroid nodule group and non-thyroid nodule group. Univariate analysis and multivariate logistic regression analysis were performed to analyze the risk factors of thyroid nodules. Results A total of 2 752 subjects were enrolled in this study, including 1 631 males and 1 121 females. The total prevalence rate of thyroid nodules was 35.6% (980/2 752), and the prevalence rate of thyroid nodules in males was significantly lower than that in females (32.5%[530/1 631] vs 40.1%[450/1 121], P<0.01). The prevalence rate of thyroid nodules increased gradually with age (P<0.01). Multivariate logistic regression analysis showed that age, obesity, fasting plasma glucose and triglyceride were independent risk factors of thyroid nodules (all P<0.05). Conclusion The prevalence of thyroid nodules maintains at a higher level in the physical examination population of Hetian County People's Hospital, and gradually increases with age. The prevalence rate in females is higher than that in males. Age, obesity, fasting plasma glucose and triglyceride are independent risk factors of thyroid nodules, and may help the early detection of thyroid nodules.