Hashimoto thyroiditis (HT) is a common autoimmune disease. Genistein is an isoflavone with immunomodulatory functions in various diseases. In this double-blind, randomized, placebo-controlled clinical study, we investigated the effects of genistein on patients with HT. A total of 218 patients were recruited. Genistein treated patients had a significant increased T-4, fr(4) levels, as well as reduction in serum TSH, TPOAb and TgAb levels, compared with those receiving placebo. Furthermore, Th1 related cytokine IFN-gamma and IL-2 changes after genistein treatment suggest the immune modulating effect of genistein is mediated through regulating the function of Thl cells. Overall, the genistein administration was effective and well tolerated in HT patients. These results demonstrate an immunological effect of genistein on HT patients. Further studies are warranted to determine the longer-term effects and possible chemopreventive effects on thyroid cancer in HT patients. (C) 2016 Elsevier GmbH. All rights reserved.