Previously we performed in vitro and in vivo studies in order to apply boron neutron capture therapy (BNCT) to the treatment of poorly differentiated (PDTC) and anaplastic thyroid carcinomas (ATC). In the present chapter, we describe the DNA damage response (DDR) induced by BNCT in thyroid cells. Also, TGFbeta/Smad independent pathway, involved in the genetic stability, and its crosstalk with DDR, were analyzed. The results obtained allowed to highlight different blocking points that could enhance the damage. Two molecules described as repair inhibitors were evaluated as possible radiosensitizers. The first one, a specific inhibitor of the enzyme Rad51: (E)-3-benzyl-2-(2-(pyridin-3-yl)vinyl) quinazolin-4(3H)-one (B02), and the second, a non-specific inhibitor of repair enzymes, sodium butyrate (NaB). Both molecules showed an increase in the efficacy of BNCT. The description of the mechanisms of action of BNCT will allow to develop new strategies to manipulate the cellular response with possible translation to the clinic.