Abstract： Objective To report the phototoxicity effects of a novel photosensitizer ZnPcS4-BSA on photodynamic therapy (PDT) towards human U251 glioma cells in vitro. Methods The cellular uptake of ZnPcS4-BSA by U251 glioma cells was quantified by UV-spectra to determine the optimal incubation time. Human U251 glioma cells were incubated with ZnPcS4-BSA of various concentrations and received laser irradiation of different energy densities. Cell survival rates were measured by CCK-8 assay.Flow cytometer was used to detect apoptosis.Gene expressions of vascular endothelial growth factor (VEGF) were detected by Real-Time PCR in the U251 cells after PDT and β-actin was used as an internal standard. The normal U251 cells severed as controls. Results The uptake of ZnPcS4-BSA by U251 glioma cells reached the maximum after incubation for 4 hours.ZnPcS4-BSA of different concentrations without laser irradiation had no significant effects on cell survival rates (P＞0.05).Without ZnPcS4-BSA incubation,compared with 0,25,50,100,200 J/cm2 groups, the cell survival rate of the 400 J/cm2 group was significantly lower (P＜0.05), whereas no significant difference was found between any other two groups. When the U251 glioma cells incubated with 30 μ mol/L ZnPcS4-BSA for 4 hours underwent laser irradiations of 25,50,100,200 J/cm2,the cellular survival rates significantly decreased with the increased energy densities (P＜0.05). When the U251 glioma cells incubated with ZnPcS4-BSA of 20,40,60,80,100 μ mol/L for 4 hours underwent laser irradiation of 200 J/cm2, the cellular inhibition rates significantly increased with the increased concentrations (P ＜0.05). Compared with controls, the cellular apoptosis and VEGF expression significantly increased in the U251 glioma cells incubated with ZnPcS4-BSA of 20 μmol/L after laser irradiation of 100 J/cm2 (P＜0.05). Conclusion The novel ZnPcS4-BSA is a good photosensitizer for PDT towards U251 glioma cells,because the ZnPcS4-BSA-mediated PDT can induce effective apoptosis of the targeted cells.