Iron oxide particles have been demonstrated previously as an effective SALDI-assisted material in SALDI MS analysis. The addition of a proton source such as citrate salts is helpful for rendering ionization efficiency. To simplify the sample preparation steps, we immobilize polyacrylic acid (PAA) onto the surface of the iron oxide particles. The modified iron oxide particles can be used as the SALDI-assisted material without the addition of extra proton source. Small biomolecules including bradykinin, melittin, and insulin are used to examine the feasibility of this approach. The results show that the SALDI mass spectral results are improved by using polyacrylic acid (MWaverage= ∼2 kDa) coated iron oxide nanoparticles.