Magnetic silica nanoparticles (MSNPs) were prepared and applied for the first time as a matrix in MALDI MS for analysis of small thermally labile biomolecules including oligosaccharides, amino acids, peptides, nucleosides, and ginsenosides. The matrix was characterized by scanning electron microscopy and UV-vis spectroscopy. It displays good performance in analyses of such biomolecules in the positive ion mode. In addition, the method generates significantly less energetic ions compared to the use of carbon nanotubes or graphene-assisted LDI MS and thus produces intact molecular ions with little or no fragmentation. In addition, the MSNPs have better surface homogeneity and better salt tolerance and cause lower noise. It is assumed that the soft ionization observed when using MSNPs as a matrix is due to the specific surface area and the homogenous surface without large clusters. The matrices were applied to the unambiguous identification and relative quantitation of the water extract of Panax ginseng roots. Any false-positive results as obtained when using graphene and carbon nanotubes as a matrix were not observed. Graphical abstract Schematic presentation of the application of magnetic silica nanoparticles in laser desorption ionization mass spectrometry. Their use results in little or no fragmentation during analysis of small labile biomolecules with some advantages such as better surface homogeneity, high salt tolerance, and lower noise.