Electrospray ionization time-of-flight mass spectrometry (ESI-TOF-MS) has been recognized as a powerful technique for studying metal clusters’ chemical composition and reaction mechanisms. It is a great challenge in mass spectrometry analysis to maintain the metal cluster molecules intact without fragmentation, which is achieved in this work by using mixed solvents to change the interaction between cluster molecules and solvent molecules, further affecting the fragmentation behaviors of the metal cluster in MS. Theoretical analysis reveals that the stability of the [(C)Au₆Ag₂(C₁₈H₁₄ONP)₆]⁴⁺ cluster in ESI-TOF-MS is related to the strength of the chemical bonds between its own atoms and the bonding between the solvent and the cluster molecules.