Background Testosterone administration was found to have a protective effect on thyroid autoimmunity in men with autoimmune (Hashimoto's) thyroiditis. Objective The present study was aimed at assessing whether oral dehydroepiandrosterone affects thyroid autoimmunity and hypothalamic-pituitary-thyroid axis activity in men with subclinical hypothyroidism induced by Hashimoto's thyroiditis. Setting The study was conducted at Medical University of Silesia, Katowice, Poland. Method The study enrolled 32 elderly men with autoimmune hypothyroidism and low dehydroepiandrosterone-sulfate levels. Based on patient preference, the participants either received oral dehydroepiandrosterone (50 mg daily; n = 16) or remained untreated (n = 16). Apart from measuring antibody titers and hormone levels, we calculated baseline and post-treatment values of three structure parameters of thyroid homeostasis. Main outcome measure Serum titers of thyroid peroxidase and thyroglobulin antibodies. Results At baseline, there were no significant differences in the investigated parameters between both groups of men. All participants completed the study. Oral dehydroepiandrosterone increased dehydroepiandrosterone-sulfate and testosterone levels, as well as had a neutral effect on estradiol levels. The increase in dehydroepiandrosterone-sulfate correlated with treatment-induced changes in serum testosterone. Moreover, dehydroepiandrosterone reduced titers of thyroid peroxidase and thyroglobulin antibodies, decreased serum thyrotropin levels, reduced Jostel's thyrotropin index as well as increased thyroid's secretory capacity. Treatment-induced changes in thyroid antibody titers, thyrotropin levels, Jostel's thyrotropin index and thyroid's secretory capacity correlated with the increase in dehydroepiandrosterone-sulfate and testosterone levels. Conclusion The obtained results show that exogenous dehydroepiandrosterone may exert a beneficial effect on thyroid autoimmunity and hypothalamic-pituitary-thyroid axis activity in men with autoimmune thyroiditis and subclinical hypothyroidism.