Plasmon enhancement of optical properties is both fundamentally important and appealing for many biological and photonic applications. Although metal-enhanced two-photon excitation fluorescence has been demonstrated in the solid substrates, there is no report on metal enhanced overall two-photon excitation fluorescence in the colloid system. Here we systematically investigated gold nanorod enhanced one- and two-photon excitation fluorescence of a porphyrin molecule, T790. The separation distance between the metal core and T790 was varied by adjusting the silica shell thickness from 13 to 42 nm. One- and two-photon excitation fluorescence intensities of T790 were found to strongly depend on the thickness of silica shell that separates gold nanorod and T790. The optimum one- and two-photon excitation fluorescence enhancement was found to occur at shell thicknesses of 34 and 20 nm, with enhancement factors of 2.1 and 11.8, respectively. Fluorescence lifetime of T790 steadily decreased as the shell thickness decreased. The observed two-photon excitation fluorescence enhancement is ascribed to a combination effect of local electric field amplification and competition between increased radiative and non-radiative decay rates. Core-shell nanoparticles that displayed enhanced two-photon excitation fluorescence were also found to exhibit significantly improved singlet oxygen generation capability under two-photon excitation. The applications of these nanoparticles as effective agents for two-photon cell imaging and nano-photosensitizers for two-photon photodynamic therapy with improved efficiency have also been demonstrated in HepG2 cancer cells. The combined advantages of enhanced two-photon excitation fluorescence and two-photon induced singlet oxygen generation make these core-shell nanoparticles as attractive agents for two-photon imaging guided two-photon photodynamic therapy.