Introduction: We aimed to investigate the role of sTWEAK in the pathogenesis of Hashimoto's thyroiditis which is a chronic inflammatory autoimmune disease. Material and methods: A total of 80 patients were included in the study; 60 of which were newly diagnosed with Hashimoto's thyroiditis (20 patients in each of the euthyroid, subclinical hypothyroid and overt hypothyroid subgroups), and 20 of which were healthy volunteers. Thyroid function tests and autoantibodies were measured using the electrochemiluminescence immunoassay method and sTWEAK, IL-17A, IL-12 and TGF-β1 were measured using enzyme-linked immunosorbent assay method. Results: The Hashimoto's Thyroiditis group had lower levels of sTWEAK and TGF-β1, but had higher levels of IL-12 and IL-17A as compared to the control group. Of these, only the difference between IL-17A levels reached the statistical significance (2.1 pg/mL vs 1.8 pg/mL, respectively; p< 0.001). While the levels of sTWEAK were similar in the control, euthyroid, and subclinical groups, the overt hypothyroidism group had lower level of sTWEAK than that of subclinical hypothyroidism (687.6 ± 153.3 pg/mL vs 888.2 ± 374.4 pg/mL, respectively; p= 0.03). A negative correlation was determined between sTWEAK level and anti-TPO (r= -0.533, p= 0.028), IL-17A (r= -0.600, p= 0.005) levels in overt hypothyroidism group. Conclusions: As a result, reduced level of sTWEAK with progression of Hashimoto's Thyroiditis and the significant correlation between the sTWEAK level and anti-TPO found in this study suggest that sTWEAK played an active role in chronic inflammation in pathogenesis of Hashimoto's Thyroiditis and in progression of autoimmunity.