An enhanced photosensitizer combining biocompatible CdSe quantum dots (QDs) with water-soluble porphyrin was synthesized by a facile method. The two photon absorption (TPA) cross-section values of the QDs range from 800 to 2 400 Goeppert–Mayer units (GM), depending on the excitation wavelength, calculated by the standard method using R6G as a reference. The singlet oxygen generation under two-photon excitation (TPE) in the QD–porphyrin system was two times greater than that in the porphyrin solution alone. This study underlines the potential of QD-based photosensitizers for biological applications in TPE photodynamic therapy.