The elevated fluoride from drinking water impacts on T3, T4 and TSH hormones. The aim was study impacts of drinking water fluoride on T3, T4 and TSH hormones inYGA (Yazd Greater Area). In this case- control study 198 cases and 213 controls were selected. Fluoride was determined by the SPADNS Colorimetric Method. T3, T4 and TSH hormones tested in the Yazd central laboratory by RIA (Radio Immuno Assay) method. The average amount of TSH and T3 hormones based on the levels of fluoride in two concentration levels 0–0.29 and 0.3–0.5 (mg/L) was statistically significant (P = 0.001 for controls and P = 0.001 for cases). In multivariate regression logistic analysis, independent variable associated with Hypothyroidism were: gender (odds ratio: 2.5, CI 95%: 1.6–3.9), family history of thyroid disease (odds ratio: 2.7, CI 95%: 1.6–4.6), exercise (odds ratio: 5.34, CI 95%: 3.2–9), Diabetes (odds ratio: 3.7, CI 95%: 1.7–8), Hypertension (odds ratio: 3.2, CI 95%: 1.3–8.2), water consumption (odds ratio: 4, CI 95%: 1.2–14). It was found that fluoride has impacts on TSH, T3 hormones even in the standard concentration of less than 0.5 mg/L. Application of standard household water purification devices was recommended for hypothyroidism.