p53 siRNA inhibits apoptosis of U2OS cells treated with azurin. The bacterial redox protein azurin selectively induces apoptosis in human osteosarcoma U2OS cells. We constructed a p53 siRNA to test the role that p53 plays in the apoptosis-inducing role of azurin in U2OS cells. Cells treated with p53 siRNA and azurin showed more viable cells, a lower apoptosis rate, lower caspase-3 activity, and up-regulation of bcl-2, downregulation of bax compared to cells treated with negative siRNA and azurin. Cells treated with negative siRNA and azurin yielded positive TUNEL dying, whereas cells treated with p53 siRNA and azurin yielded few positive cells. These results suggested that p53 siRNA was capable of inhibi-ting the apoptosis induced by azurin 2 days after treatment with p53 siRNA and azurin. Azurin may induce apoptosis through combination with p53. The decrease in p53 protein levels did not inhibit cell apoptosis rates, but rather increased these rates in U2OS osteosarcoma cells 3 days after treatment with p53 siRNA. Since U2OS cells are p53 wild-type cancer cells, p53 potentially acts as an oncogene in U2OS osteosarcoma cells. Treatment with azurin may transform the function of p53 from inhibiting to inducing apoptosis.