NW16 is an orally active inhibitor for STAT3 with K d of 11.0 μM. NW16 arrests the cell cycle at S phase, induces apoptosis in HCT116, and inhibits the proliferation of cancer cell HCT116, A549, and B16 with IC 50 s of 0.28, 1.22, and 9.86 μM, respectively. NW16 induces the production of ROS , inhibits the PI3K/AKT signaling pathway, and thus exhibits antitumor efficacy in mouse model.