Photodynamic therapy (PDT) has become one of the popular treatment modalities for the management of cancer and other diseases. PDT in combination with conventional chemotherapy has shown an enhanced efficacy in combating different types of cancers. In this present study, we investigated the cytotoxic and apoptotic effects of genistein in combination with photofrin induced PDT in an ovarian cancer cell line SK-OV-3. Cells were treated with different concentrations of genistein (0, 25, 50, and 100μM) in combination with 3.13μg/ml and 6.25 μg/ml of phtofrin induced PDT. The viabilities of the cells were decreased by 34.5% and 49.0% respectively with the different concentrations of photofrin in PDT. In order to investigate whether genistein in combination with PDT can induce apoptotis, SK-OV-3 cells were stained with hoechst 33342 and propidium iodide. From the microscopic images, it was observed that apoptosis was induced in the SK-OV-3 cells treated with either genistein (100μM) or PDT alone. In addition, different apoptosis related proteins like caspase-8, caspase-9, caspase-3, cytochrome c and PARP were also activated when the cells were treated with the combination of genistein and PDT. These results show that the general apoptotic pathway requiring caspase-3 activation through caspase-8 is the main pathway that induces apoptosis in SK-OV-3 cells. Therefore, we conclude that genistein sensitizes the activity of photodynamic therapy by photofrin in SK-OV-3 cells by inducing apoptosis through the activation of caspase-8 and caspase-3.