Time-of-flight secondary ion mass spectrometry(ToF-SIMS)is a well-established but rapidly evolving surface and interface analysis technique that provides chemical information(m/z)by collecting ejected secondary ions when primary ions impinge onto the sample surface.[1] It has become an important and powerful tool for chemical imaging of elements and molecules.By performing dual-beam strategy that is one beam for analysis and one beam for sputtering,3-dimension images can be obtained.Recently,ToF-SIMS has been applied for surface and interface analysis of biological samples due to its high spatial resolution,high sensitivity and chemical specificity.[2] In our work,we investigated the distributions of several metal(Pt or Ru)anti-cancer complexes at single cell level by ToF-SIMS.From the results,it indicated that at the early stage(~2h-3h)of incubation,the complexes targeting to EGFR mainly localized at the cell membrane.When the incubation was prolonged to 24 h,more complexes could enter the nucleus and bind to DNA.These results verify the dual-targeting features of the selected complexes.We also studied the interaction between DNA damaged by cisplatin and endogenous HMGB1 protein in HeLa cells using TOF-SIMS combined with confocal fluorescence microscopy.Our results showed that Pt signal from ToF-SIMS is partially overlapped with HMGB1 image from confocal fluorescence microscopy in the nucleus,proving that the DNA damaged by cisplatin can recruit HMGB1 to prevent the repair nuclease from recovering DNA damage.