Utilizing a customized multiple-ion laminar flow tube reactor in tandem with a triple quadrupole mass spectrometer, we report a study of the gas-phase reactivity of Ag-n(+) clusters with acetylene. Well-resolved Ag-n(+) clusters (n = 1-20) are produced by a self-designed magnetron sputtering source (MagS); however, on their reactions with acetylene under sufficient collisional conditions, only Ag-7(+)[C2H2] is produced with a reasonable intensity. DFT calculations reveal that Ag-n(+) clusters do not form strong Ag-C bonds with C2H2 and Ag-7(+)[C2H2] bears larger binding energy than the other Ag-n(+)[C2H2] although within similar cluster-pi interactions. Besides gas-phase reaction rate estimation, the relatively large noncovalent cluster-pi interaction in Ag-7(+)[C2H2] is fully demonstrated via topological analysis and natural bonding orbital analysis. Also, we illustrate both thermodynamically and kinetically favored channels in producing the Ag-7(+)[C2H2]. This study helps in understanding metal-involved noncovalent bonds and how such weak interactions are able to tune the material function and biological activity.