Interleukin IL-23 receptor (IL-23R) is increasingly recognized as a key checkpoint in autoimmune diseases, including Hashimoto's thyroiditis (HT). However, the molecular mechanisms regulating IL-23R expression are still unknown. MicroRNAs have emerged as key regulators of various biological events via suppressing target mRNAs at the posttranscriptional level. In this study, we found that the IL-23R mRNA expression was increased in peripheral blood mononuclear cells from HT patients, and there was a positive correlation between the level of IL-23R mRNA and the serum level of anti-thyroglobulin antibody (TgAb). The miR-125a-3p expression was decreased and inversely correlated with elevated level of IL-23R in patients with HT. MiR-125a-3p inhibited IL-23R expression through directly targeting 3'untranslated region of IL-23R. An inverse correlation was observed between the level of miR-125a-3p and serum level of TgAb. Furthermore, we also found upregulated IL-23R expression and downregulated miR-125a-3p expression in thyroid tissues from HT patients. Taken together, our results indicate that decreased expression of miR-125a-3p was involved in the pathogenesis of Hashimoto's thyroiditis.