Radiation exposure during space missions represents a major threat for human health, affecting all body organs and tissues. Regarding thyroid function, it has been shown that ultraviolet radiation (UV-C) has dose-dependent apoptotic effects on FRTL-5 cells, a normal strain of rat thyrocytes. The present study examined the effects of a sub-lethal dose of UV-C on FRTL-5 cell growth and gene expression. Cells exposed to 10 J/m2 UV-C showed no differences in viability compared to control cells after 24 h, but the BrdU incorporation was reduced, indicating a cytostatic effect. Quantitative RT-PCR carried out at 24 h and 48 h after irradiation demonstrated that the mRNA levels of thyroglobulin (Tg), thyroperoxidase (Tpo) and sodium/iodide symporter (Nis) were transiently decreased at 24 h in treated cells, while the mRNAs of the thyroid transcription factors, TTF1, Foxe1 and Pax-8, were not affected. In cells cultured with TSH-free medium, the basal transcription of Tg, Tpo and Nis genes was equally impaired by radiation, and no longer stimulated by TSH. In conclusion, the results demonstrated that a sub-apoptotic dose of UV-C compromises not only thyrocyte proliferation, but also the expression of genes involved in thyroid hormone production. These findings might contribute to explaining the histological, biochemical and clinical features of hypothyroidism observed in both animals and humans during space flight.