Secondary Ion Mass Spectrometry (SIMS) with Gas Cluster Ion Beams (GCIB) wasstudied with experiments and molecular dynamics (MD) simulations to achievea high-resolution depth profiling. For this purpose, it is important toprevent both ion-mixing and the surface roughening due to energetic ions. Asthe Ar cluster ion beam shows surface smoothing effects and highsecondary-ion yield in the low-energy regime, the cluster ion beam would besuitable for the primary ion beam of SIMS. From MD simulations of Ar clusterion impact on a Si substrate, the ion-mixing is heavier than for Ar monomerions at the same energy per atom, because the energy density at the impactpoint by clusters is extremely high. However, the sputtering yields with Arcluster ions are one or two orders of magnitude higher than that with Armonomer ions at the same energy per atom. Comparing at the ion energy wherethe ion-mixing depths are the same by both cluster and monomer ion impacts,cluster ions show almost ten times higher sputtering yield than Ar monomerions. Preliminary experiment was done with a conventional SIMS detector anda mass resolution of several nm was achieved with Ar cluster ions as aprimary ion beam.