Suppression of HMGB3 expression inhibits cell viability, promotes cell apoptosis and cell cycle arrest, and suppresses cell migration and invasion in thyroid cancer. Cytoplasmic HMGB3 activates nucleic acid-mediated TLR3/NF-κB signaling, and extracellular HMGB3 interacts with the transmembrane receptor TREM1 in PTC. The gene discussed is TLR3; the disease is thyroid cancer.