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