Despite the challenges in identifying earthquake precursors in intraplate (inland) earthquakes, various hydrological and geochemical measurements have been conducted to establish a possible link to seismic activities. Anomalous increases in radon (222Rn) concentration in soil, groundwater, and atmosphere have been reported prior to large earthquakes. Although the radon concentration in the atmosphere is lower than that in groundwater and soils, a recent statistical analysis has suggested that the average atmospheric concentration over a relatively wide area reflects crustal deformation. However, no study has sought to determine the underlying physico-chemical relationships between crustal deformation and anomalous atmospheric radon concentrations. Here, we show a significant decrease in the atmospheric radon concentration temporally linked to the seismic quiescence before the 2018 Northern Osaka earthquake occurring at a hidden fault with complex rupture dynamics. During seismic quiescence, deep-seated sedimentary layers in Osaka Basin, which might be the main sources of radon, become less damaged and fractured. The reduction in damage leads to a decrease in radon exhalation to the atmosphere near the fault, causing the preseismic radon decrease in the atmosphere. Herein, we highlight the necessity of continuous monitoring of the atmospheric radon concentration, combined with statistical anomaly detection method, to evaluate future seismic risks.