Hard-Soft Acid-Base (HSAB) principle plays an important guiding role in the design and synthesis of novel clusters and coordination compounds, in which "soft acids prefer to react with soft bases, while hard acids have an affinity for hard bases". Based on HSAB principle, four Ag/Ti heterometallic clusters, including Ag2Ti10, Ag2Ti11 with "Ti-encapsulated Ag" configurations, and two "Ag-encapsulated Ti" structures Ag2Ti2 and Ag2Ti12, were synthesized under solvothermal conditions. In addition, Ag2Ti12 exhibited an efficient and stable catalytic activity for sulfide oxidation. This work provides not only a new structural model for the modulation of the catalytic oxidative desulfurization properties of Ag/Ti heterometallic clusters but also a new insight of the utilization of phosphine-containing ligands to regulate the structure of Ag/Ti heterometallic clusters.