Synthetic oligodeoxynucleotides (ODN) expressing CpG motifs (CpG-ODN) mimic the immunostimulatory activity of bacterial DNA and are commonly used to activate Toll like receptor9 (TLR9) for therapeutic applications. CpG-ODN can counteract the activity of DNA-damaging chemotherapy and radiation therapy on immune cell and enhance immunity in preclinical mouse models. We hypothesized that these actions of CpG-ODN on immune cells are expressed by modulation of DNA repair genes . We conducted a PCR array analysis of DNA repair genes expression in splenocytes obtained from mice injected intraperitoneally with CpG-ODN and/or Cisplatin. CpG-ODN modulate expression of DNA repairing genes inducing down regulation in most of DNA repairing genes but up regulate some genes participate in biological process suggesting its role in it. Cisplatin had an effect on expression of DNA repairing genes inducing up regulation of most genes implicated in repair of toxic effect of Cisplatin. We concluded that the effect of CpG-ODN in elimination of DNA damaging activity of Cisplatin on immune cells appear as counteracting and normalizing the modulation of repair genes expression occurred by Cisplatin.