Exploring efficient and robust electrochemiluminescence (ECL) performance of liposoluble porphyrins in aqueous phase for analytical purposes especially for important biological targets is still very challenging. In this work, a novel depolymerization-induced electrochemiluminescence (DIECL) of porphyrin and β-cyclodextrin (β-CD) self-assembly through a coreactant route was discovered. Among the studied meso-tetrasubstituted porphyrins, self-assembly of 5,10,15,20-tetrakis(4-hydroxyphenyl) porphyrin (THPP) and β-CD (THPP@β-CD) exhibits the best DIECL behavior with high efficiency (21.8%) as well as good reproducibility and stability. A mechanistic study suggests that the facile complexation of porphyrins with amphiphilic β-CD via hydrogen bonding interaction greatly improves the water insolubility and the aggregation-caused deficient ECL of liposoluble porphyrins in aqueous solution. Furthermore, because of the strong hydrogen bonding between the hydroxyl groups on THPP@β-CD and a highly electronegative substrate, such THPP@β-CD is found to serve as an efficient luminophore for recognition of most electronegative fluoride (F-) in the aqueous phase with high sensitivity and selectivity, together with a low limit of detection (0.74 μΜ). The simplicity of this THPP@β-CD and its unique DIECL property in current work provides a new guide for the ECL applications of liposoluble porphyrins in aqueous phase.