Potassium bromide (KBrO₃) is widely used in bread production, cosmetics and water disinfection. KBrO₃ is a DNA oxidizing agent that induces base modifications as 8-Oxo-deoxyguanosine (8-oxodG), also induces chromosomal aberrations, micronuclei and γH2AX foci which are the endpoints of DNA double-strand breaks (DSBs). Therefore, the cytotoxic and genotoxic effects of KBrO₃ are mainly related to DNA damage. Conversely, the role of DNA damage in the cytotoxic effects of KBrO₃ has been poorly understood in conjunction with that of protein damage. Herein, we illustrated the cytotoxic effects of KBrO₃ through DNA damage-dependent and DNA damage-independent mechanisms. For this proof of concept, we analyzed the sensitivity of DNA repair-proficient and –deficient cells and subsequently measure DNA and protein damage after treatment with KBrO₃. Our results show that the DNA repair genes DNA-PKcs, XRCC3 and RAD51D are strongly required for cell survival and essential to alleviate the cytotoxic effect of KBrO₃. The quantitative analysis of DSBs upon treatment with KBrO₃ shows a significant increase in the yields of DSBs suggesting that DSBs are critical DNA damage induced by KBrO₃ and accounts for DNA damage-dependent cytotoxicity. Furthermore, thioredoxin 1 oxidation was not observed upon treatment with potassium bromide, strongly exclude the involvement of DNA damage-independent cytotoxicity based on protein damage. Based on the current findings we suggested a mechanistic model of bromate cytotoxicity that is mediated by DNA but not protein damage.