Abstract: Objective To analyze the detection rate of thyroid nodules and its influencing factors among individuals undergoing routine health check-up in Guangdong Province. Methods We analyzed the results of thyroid ultrasonography of 309 576 individuals receiving routine health check-up in a general hospital in Guangdong Province over the past 10 years. The data were compared between the individuals with and without thyroid nodules using two independent samples t test, MannWhitney U test and Chi-square test. Binary logistic regression was used to analyze the relationship between different factors and thyroid nodules, and the odds ratio (OR) and 95% confidence interval (95% CI) were calculated. Results Based on the structured and standardized data, the total detection rate of thyroid nodules was 9.68% among the individuals, 7.71% in male and 13.51% in female subjects, showing a significant gender difference (χ2=2677.08, P<0.001). In the overall population, the detection rates of thyroid nodules gradually increased with age, but in each age group, the detection rate remained significantly higher in female subjects than in male subjects (P<0.001). The subjects with thyroid nodules showed a significant higher percentage of male gender, an older age, a greater BMI, and significantly higher SBP, DBP, FBG, TC, LDL-C, HDL-C, TG as well as higher detection rates of fatty liver, hyperlipidemia, hyperglycemia, and metabolic syndrome than those without thyroid nodules (all P<0.001). Binary logistic regression analysis showed that thyroid nodules were significantly associated with gender (OR=0.455, 95%CI: 0.443-0.468), age (45-59 years: OR=1.660, 95%CI: 1.613-1.710; ≥60 years: OR=3.329, 95%CI: 3.202- 3.462), BMI (underweight: OR=0.808, 95%CI: 0.755-0.864; overweight: OR=1.074, 95%CI: 1.038-1.112; obesity: OR=1.281, 95%CI: 1.221-1.343), hyperlipidemia (OR=1.053, 95%CI:1.022-1.085), high blood glucose (OR=1.177, 95%CI: 1.105-1.252), and metabolic syndrome (OR=1.111, 95%CI: 1.071-1.152). Conclusion The detection rate of thyroid nodule is much higher in female than in male individuals in Guangdong Province and is significantly associated with gender, age, BMI and metabolic related diseases. Male gender and underweight might be protective factors for thyroid nodules, while an advanced age, overweight/obesity, hyperlipidemia, high blood glucose and metabolic syndrome are associated with an increased risk of thyroid nodules. Thyroid ultrasound examination is recommended in routine health check-up for early detection and treatment of thyroid diseases.