Abstract: The separation of intact protein mixture by two dimensional gel electrophoreses following MALDI-TOF-MS analysis is a powerful tool in proteomics research. Although MALDI-TOF-MS has some tolerance to salt in peptide or protein mixtures, high salt concentration will degrade the signal of mass spectra. To address this issue, a new method for desalting of peptide or protein mixture by Fe₃O₄/ TiO₂ nanoparticles on the MALDI target following MALDI-TOF-MS analysis was established. Experimental results showed that 10 fmol/100 fmol myoglobin in 3 M/10 Murea solution can be identified by the method. Replicate experiments suggest that this new desalting method is simple, rapid and high throughput technique in gel-based proteomics study.