Monitoring sulfur dioxide (SO2) is crucial for protecting human health as exposure to this pollutant can cause respiratory and cardiovascular illnesses, particularly in vulnerable populations. The primary materials currently used for detecting SO2 are metal oxides. However, it is still a challenge to detect SO2 at the parts per billion (ppb) level via these materials even when operated at high temperatures. Herein, we propose a highly sensitive SO2 sensor that operates at room temperature (RT). The sensing material employed is the hydrothermally synthesized bismuth oxyselenide (Bi2O2Se) nanosheets. The Bi2O2Se sensor exhibits a response value of 34% to 1 ppm SO2 and a detection limit of 20 ppb, which surpasses most SO2 sensors reported to date. The superior sensitivity and selectivity of Bi2O2Se nanoppbsheets toward SO2 are attributed to their strong adsorption energy (-0.76 eV) and significant electron transfer (2.205 e) between Bi2O2Se and SO2 molecules, as confirmed by density functional theory (DFT) calculations. Finally, a wireless SO2 sensing system is designed and implemented based on the SO2 sensor, enabling the detection of trace-level SO2 in indoor environments such as factories and laboratories, thereby protecting the well-being of personal further.