As a new member of the gaseous regulators, sulfur dioxide (SO2) plays a crucial role in many biological activities. Recent studies have shown that SO2 is capable of inducing cancer cell apoptosis by regulating intracellular reactive oxygen species (ROS), allowing SO2 to serve as an efficient therapeutic agent. Although various polymer-based platforms have presented great potential for the controlled release of SO2, most of the systems are incapable of monitoring the intracellular generation of SO2. In this work we present the rational design of SO2-releasing biodegradable polymersomes, accompanied by a self-reporting property. The polymersome consists of a hydrophilic block of poly(ethylene glycol) (PEG) and a hydrophobic segment of poly(trimethylene carbonate) (PTMC)-based SO2 donors. The polymersomes not only exhibit good SO2-releasing performance upon treatment with glutathione (GSH), but can also regulate the fluorescence change of the system, offering a good platform for real-time monitoring of the intracellular production of SO2. Significantly, the in vitro and in vivo studies indicate the potential for exploitation of these polymersomes as antitumor agents. We expect that incorporating both the SO2-releasing capacity and self-reporting feature within a polymersome system will provide a unique opportunity for the development of intelligent gas nanovehicles.