Background: Anaplastic thyroid cancer (ATC) is an undifferentiated, aggressive malignancy, for which there are no effective therapies. Though ATCs only make up less than 2% of all thyroid cancer cases, they represent over half of the thyroid cancer-related deaths. Chrysin, a natural flavonoid, has recently been reported as a potential anti-cancer agent. However, the effect of this compound on ATC cells is not known. Thus, in this study, we evaluated the antiproliferative nature of chrysin in ATC cells. Methods: HTH7 and KAT18 cells, derived from patients with ATC, were treated with chrysin (25-50 μM) for up to 6 d. Cell proliferation was measured every 2 d using the 3-(4,5- dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT). Western blot analysis for molecular makers of apoptosis was carried out to investigate the effect and mechanism of Chrysin on ATC. Results: Chrysin inhibited proliferation of HTH7 and KAT18 in a dose-and time-dependent manner. HTH7 and KAT18 cells with Chrysin treatment showed a significant increase in cleaved caspase-3, cleaved PolyADP Ribose Polymerase (PARP), along with a decrease in cyclin D1, Mcl-1, and XIAP. Furthermore, the ratio of Bax to Bcl-2 expression in ATC cells revealed an increase after the treatment. Conclusions: Chrysin inhibits growth in ATC cells via apoptosis in vitro. Therefore, the natural flavonoid chrysin warrants further clinical investigation as a new potential drug for the treatment for ATC. © 2011 Elsevier Inc. All rights reserved.