Objective: To investigate the photodynamic effect of photosensitizer PsD-007 on human hepatocellular HepG2 cells in vitro and its mechanism. Methods: HepG2 cells were divided into three photodynamic treatment groups, which were incubated with 10, 20 and 30 μg/mL PsD-007 respectively, and were all irradiated with visible light at 630 nm (energy density was 6.0 J/cm2 and exposure time was 2 min) during incubation. Meanwhile, three control groups were used, namely, the blank control group, irradiation alone group and dark cytotoxic group (treated with 30 μg/mL PsD-007 alone without irradiation). Twenty-four hours after experiment, the cell survival rates of each group were detected by MTT assay, and their apoptosis cells were observed by using apoptosis detection kit and fluorescence microscopy. The gene and protein expression of caspase-3, caspase-8 and P53 in cells of the two photodynamic treatment groups (20 and 30 μg/mL PsD-007) and three control groups were determined by Real-time PCR and Western blot method, respectively. Results: Compared with the blank control group, the cell survival rates of the three photodynamic treatment groups significantly decreased in a concentration-dependent manner (all P<0.05), while those of the irradiation alone group and dark cytotoxic group showed no obvious change (P>0.05). The fluorescence microscopic observation revealed that the late apoptotic and necrotic cells remarkably increased in each photodynamic treatment group compared with the three control groups. The Real-time PCR and Western blot results showed that both gene and protein expression levels of caspase-3, caspase-8 and P53 in the cells of the two photodynamic treatment groups were significantly higher than those of the three control groups. Conclusion: PsD-007 has photodynamic cytotoxic effect on HepG2 cells in vitro, and the mechanism is probably related to the regulation of caspase and p53 expression that thereby induces the cell apoptosis and necrosis.