Protein affinity is of importance for porphyrins in their application in photodynamic therapy (PDT). A new Phenol Red-modified porphyrin (R-TPP) was designed and synthesized to fully take advantage of the binding character of Phenol Red towards protein. Detailed comparisons of absorption spectra, fluorescence spectra, n-octanol/water partition coefficients, ¹O₂ quantum yields, as well as protein photocleaving abilities between R-TPP and its parent porphyrin Br-TPP clearly demonstrate the benefits stemming from the modification of Phenol Red. On one hand, the presence of Phenol Red moiety greatly enhances the binding affinity of R-TPP towards model proteins (bovine serum albumin and hen egg lysozyme), and therefore improves the availability of ¹O₂. On the other hand, the presence of Phenol Red moiety provides R-TPP with amphiphilic character, and therefore restricts aggregation and favors the generation of ¹O₂. As a result, R-TPP photocleaves proteins efficiently, showing promising application potential in PDT.