A detailed analysis of benzofuranone compounds under multiple tandem mass spectrometry (ESI-MS(n)) conditions is reported. Element composition data of the fragment ions were obtained with the aid of comparison of the multiple tandem mass spectra of four compounds, and the structures of which are identical except for some substituted groups or epimers or ra-r/ww-isomers. Attempts have been made to provide rational pathways for the formation of the fragment ions from these protonated compounds. And the structure-fragmentation relationships will facilitate the characterization of the structures of other analogs.