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Abstract: Synthetic Oligodeoxynucleotides (ODN) expressing CpG motifs (CpG-ODN) mimic the immunostimulatory activity of bacterial DNA and are commonly used to activate Toll Like Receptor 9 (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 processes suggesting the role of CpG-ODN in these processes. 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 conclude