BACKGROUND: Photodynamic therapy (PDT) uses a photosensitizer and light to destroy abnormal cells. Talaporfin sodium (NPe6) is a second-generation photosensitizer. METHODS: We evaluated the toxic effects of different combinations of laser and NPe6 doses on squamous cell carcinoma (KLN205) and sarcoma (Meth A) cell lines. The cells were incubated with 0, 5, 10, or 30μg/mL NPe6 for 24h. The cells were then irradiated with 0, 5, 15, or 30mW/cm2 of laser power, and 0, 1, 5, 10, or 20J/cm2 of laser energy. Cell viability was evaluated after 24h. We also evaluated the cytotoxic effects of continuous wave or square-wave modulated laser irradiations (2, 5, or 10Hz, 50% duty) on Meth A cells. RESULTS: The median lethal doses of NPe6 against the KLN205 and Meth A cells after treatment at a fluence rate of 15mW/cm2 and a light dose of 20J/cm2 were 18.6 and 5.0μg/mL, respectively. Meth A cells were more sensitive to PDT than KLN205 cells. There was no significant difference between the effects of continuous wave and square-wave modulated lasers on Meth A cell viability. CONCLUSIONS: NPe6 PDT induced cell death in a dose-dependent manner in KLN205 and Meth A cells. More work is required to evaluate the cytotoxic effects of square-wave modulated laser therapy at low light doses.