Photodynamic therapy (PDT) is a potential treatment method that has proven to be an efficient, safe, and minimally invasive technique. The technique mainly depends on photosensitizes to produce reactive oxygen species underthe irradiation of specific wavelengthlight, therefore causing specific killing to tumor cells and tissues. Among them, hematoporphyrinmonomethyl ether (HMME) mediated PDT has been used in clinical treatment of port wine stain (PWS) due to its single component, high yield of singlet oxygen and short light-sensitive period. In order to improve the efficiency of the PDT, we synthesized stable, monodispersecation Au nanospheres with absorption peak of 530 nm based on seed-growth. Poly-(sodium 4-styrenesulfonate) (PSS) was employed to modify Au nanospheres owing to its low toxicity and strong anion electrolytic activation. Then TiOH2+ coming from TiCl3 hydrolysis could be closely attached to negatively charged Au nanospheres through electrostatic attraction and further oxidation to obtain AuNP@TiO2 core-shell nanostructure. The TiO2 shell thickness could be adjusted by changing the NaHCO3 amount, then further mixing AuNP@TiO2 core-shell and HMME to form the conjugate. The obtained samples were characterized by UV-visible absorption spectroscopy, infrared spectroscopy, laser nanoparticle size analyzer and transmission electron microscope (TEM). The results showed that the core-shell nanostructures were stable and well-distributed. Otherwise, the cell killing experiments were performed with KB cells and LED array of 510 nm light source, and CKK-8 was used to evaluate the cell viability. The results showed that the conjugate improved PDT efficiency about 35% higher than that of HMME alone.