We show that (i) PAK4 critically contributes to the radiosensitivity and invasion of glioblastoma cells, (ii) PAK4 knockdown and pharmacological targeting elicit radiosensitization along with increased DNA damage, and (iii) PAK4 modulates the expression and phosphorylation of the key DNA repair proteins ATM, DNA-PK, Rad51, and PARP1. Here, PRKDC is linked to glioblastoma.