Analysis using publicly available algorithms has found that high mobility group AT-hook 2 (HMGA2), a key transcriptional regulatory factor, is a potential target of microRNA-204 (miR-204). Some studies have shown that both miR-204 and HMGA2 are associated with cancer development. We examined the possible relationship between miR-204 and HMGA2 in the development of thyroid cancer. We assessed miR-204 expression in thyroid cancer specimens and cell lines using real-time polymerase chain reaction (PCR). Luciferase reporter assay was used to confirm the target associations. The effect of miR-204 on cell proliferation was confirmed with tetrazolium and colony formation assays. Gene and protein expression were examined using real-time PCR and western blotting, respectively. MiR-204 was downregulated in the thyroid cancer specimens and cell lines, and targeted the 3^\prime untranslated region of HMGA2 directly. MiR-204 overexpression decreased cyclin D1 and Ki67 expression and increased P21 expression, which subsequently inhibited thyroid cancer cell proliferation. Our findings suggest that miR-204 plays a protective role by inhibiting thyroid cancer cell proliferation, and may identify new targets for anti-cancer treatment.