Current cancer therapy has been restricted by the hypoxic microenvironment of tumors, especially for strongly oxygen-dependent photodynamic therapy. To defeat tumor hypoxia, an oxygen-irrelevant radical nanogenerator, PI/FBC, is developed by the co-assembly of iodized polymer PI and NIR photosensitizer FBC, and further evaluated as a remote controllable free radical generation platform for enhancing antitumor efficiency. The PI/FBC radical nanogenerator can be excited by NIR light to produce ROS through transfer of energy to oxygen and induce the formation of toxic iodine radicals via electron transfer to PI. Notably, unlike conventional tumor treatments, such a radical nanogenerator is controllable and insusceptible to oxygen concentration. Moreover, benefiting from the strong NIR emission of FBC, the distribution of the PI/FBC radical nanogenerator can be monitored without incorporating other imaging agents. This PI/FBC radical nanogenerator treatment will no doubt broaden the family of antitumor strategies by using non-oxygen radicals, which is significant for reference in the development of promising anticancer agents.