This study aims to assess the applicability of the serum iodine (SI) standards proposed by the WHO and other renowned laboratories for the Chinese population. Additionally, it seeks to establish reference intervals (RIs) for SI in Chinese adults and conduct a risk assessment between serum iodine concentration (SIC) and the development of thyroid diseases. This study enrolled 3138 adults aged 18-60 years from six provinces in China. A total of 1794 healthy adults with normal thyroid function were selected to assess the applicability of the international standards and establish China's RI, utilizing five external datasets for validation. Multiple logistic regression analysis was applied to explore the relationship between SIC and thyroid disease. The ratios of adults with normal thyroid function from five provinces whose SI levels fall outside the limits of the international standards are partially greater than 10%. China's RI was 40.11-97.59 µg/L, and the ratios of individuals in the validation datasets outside this RI were all less than 10%. Adults with low SIC levels (<
40.11 µg/L) were at higher risk of hypothyroxinemia (adjusted OR = 4.715, 95% CI = 1.459-15.235), overt hypothyroidism (adjusted OR = 4.719, 95% CI = 1.583-14.067), and autoimmune thyroiditis (adjusted OR = 2.394, 95% CI = 1.410-4.064). Adults with high SIC levels (>
97.59 µg/L) were at a higher risk of overt hyperthyroidism (adjusted OR = 18.170, 95% CI = 5.940-55.577). These international standards are not fully applicable to the Chinese population. We established RIs for SI in Chinese adults to better accommodate the country's specific conditions.