<p>The aim of this study was to investigate the prevalence of thyroid nodule and its association with triglyceride-glucose index (TyG) in Western Liaoning Province of China. A cross-sectional survey was conducted in six counties under the jurisdiction of Huludao, Fuxin, and Chaoyang in Liaoning Province from 2019 to 2022. All the subjects who underwent thyroid B-ultrasound and related biochemical tests were recruited. TyG was calculated using fasting triglycerides and plasma glucose. A total of 2374 subjects were included, of which 583 (24.6%) were found to have thyroid nodules. The results of multivariate regression analysis indicated that a higher quartile of TyG was an independent risk factor for thyroid nodule. The results of subgroup analysis suggested that the above association was more explicit in younger subjects, non-smokers, highly educated or high-income groups, and non-iodine-deficient subjects. Similar findings were demonstrated in subjects with solitary or multiple thyroid nodules. Our study suggested for the first time that a higher TyG level is the risk factor for thyroid nodule, and the association between the two is more explicit in specific populations. It is recommended that people with high TyG levels should pay more attention to the regular screening of TN.</p>