To summarize, our data show that MRE11 rs2155209 TT, XRCC5 rs828907 T, RAD51 rs1801321 GG, rs12593359 GG, LIG4 rs1805388 GG, CHEK1 rs558351 TT, TP53 rs1042522 CC, ATM rs1801516 A, XRCC6 rs2267437 CC and NBN rs2735383 GG independently predict an unfavorable clinical outcome in HNSCC patients receiving DNA-damaging therapy. Here, XRCC6 is linked to head and neck squamous cell carcinoma.