The　development　of　cisplatin　and　Pt-based　analogues　anticancer　agents　requires　knowledge　concerning　the　molecular　mechanisms　of　interaction　between　such　drugs　with　DNA.　However,　the　binding　dynamics　and　kinetics　of　cisplatin　reactions　with　DNA　determined　by　traditional　approaches　are　far　from　satisfactory.　In　this　study,　a　typical　20-base　oligonucleotide　(CGTGACAGTTATTGCAGGCG),　as　a　simplified　model　representing　DNA,　was　mixed　with　cisplatin　in　different　molar　ratios　and　incubation　time.　High-resolution　XPS　spectra　of　the　core　elements　C,　N,　O,　P,　and　Cl　were　recorded　to　explore　the　interaction　between　cisplatin　and　DNA.　From　deconvoluted　Cl　spectra　we　could　readily　differentiate　the　covalently　bound　chlorine　from　ionic　chloride　species　in　the　cisplatin-oligo　complexes,　which　displayed　distinct　features　at　various　reaction　times　and　ratios.　Monitoring　the　magnitude　and　energy　of　the　photoelectron　Cl　2p　signal　by　XPS　could　act　as　a　sensitive　marker　to　probe　the　interaction　dynamics　of　chemical　bonds　in　the　reaction　of　cisplatin　with　DNA.　At　37°C,　the　optimum　incubation　time　to　obtain　a　stable　cisplatin-oligo　complex　lies　around　20　hrs.　This　novel　analysis　technique　could　have　valuable　implications　to　understand　the　fundamental　mechanism　of　cisplatin　cytotoxicity　and　determine　the　efficiency　of　the　bonds　in　treated　cancer　cells.　©　2012　Fangxing　Xiao　et　al.