Objective To identify the effects of human thyroid receptor interacting protein 15 (hTRIP 15) on the function of thyroid receptor (TR). Methods Fusion protein, protein translation in vitro and glutathione -S- transferase (GST) pulldown assay were used for identification of protein-protein interaction, and gel-shift assay for protein-DNA interaction. Results Molecular weight of hTRIP 15 fusion proteins expressed in E coli and TRα translated in vitro matched with that predicted. hTRIP 15 and its N terminal could interact with TRα. hTRIP15 inhibited binding of TR and thyroid response element (TRE), with more significant inhibition using high dose of hTRIP 15. Conclusion hTRIP 15 regulates transcription of the target genes of TR as a corepressor. TR-binding domain is in hTRIP15 N terminal,and the C terminal may be the regulatory domain.