Transition metal oxide ZnO nanoparticles as inorganic matrix was adopted in the matrix assisted laser desorption ionization time-of-flight mass spectrometry ( MALDI-TOF-MS ) analysis of small molecule compounds including sugars and stearic acid and its performances were investigated. In addition, the feasibility of metal ion selective ionization of L-arginine by using NiO and CuO nanoparticles as matrix directly was explored initially. In the experiment, the analyte and nanoparticle suspension were mixed on the sample plate. The crystal of analyte and matrix was excited by 337 nm laser after the solvent was evaporated, and then detected under reflection mode of TOF-MS. The results indicated that ZnO nanoparticles with high UV absorption could eliminate the interference of conventional matrix, simplify the mass spectra, and enhance the peak intensity of stearic acid under negative mode. Moreover, Cu+ ion selective ionization of L-arginine was achieved in comparison of CuO and NiO as matrix for MALDI-TOF-MS analysis of L-arginine.