Photodynamic therapy (PDT) is a treatment utilizing the generation of singlet oxygen and other reactive oxygen species (ROS), which selectively accumulate in target cells. Peroxiredoxin (prx) plays an important role in eliminating peroxides generated during metabolism. Prx exert protective antioxidant role in cells though peroxidase activity. The aim of present work is to investigate the cytotoxicity of photofrin-mediated PDT in prx IV-transfectant AMC-HN3 cell lines. We confirmed that PDT has an effect on ROS generation in prx IV-induced cell lines. Treatment of PDT in prx IV-HN3 cell lines inhibits cytotoxic effects. Prx IV-induced HN3 cell lines resists in cell death during PDT. Also, prx IV-HN3 cell lines treated PDT inhibited ROS generation in contrast with vector control. We indicated that prx IV-induced AMC-HN3 cell lines have a function as inhibitors during PDT.