Abstract: Cancer is a malignant disease that threatens human’s lives. Organometallic ruthenium complexes have exhibited cytotoxic to cancer cells including cisplatinum-resistant cancer cells in vitro and in vivo. As to cisplatin, DNA is also a potential target to organoruthenium complexes, but ruthenium complexes have been shown less side-effect in vitro. The present work focused on investigating the interactions between organometallic ruthenium complexes and oligonucleotides, which can be recognized by high mobility group protein box 1 (HMGB1) and in turn trigger downstream signal transduction, using LC-MS. The results will be helpful to understand the mechanism of action of the organoruthenium complexes.