Human epidemiological studies showed that radon and arsenic exposures are major risk factors for lung cancer in Yunnan tin miners. However, biological evidence for this phenomenon is absent. In this study, HBE cells were exposed to different concentrations of sodium arsenite, different radon exposure times, or a combination of these two factors. The results showed a synergistic effect of radon and sodium arsenite in cell cytotoxicity as determined by cell viability. Elevated intracellular ROS levels and increased DNA damage indexed by comet assay and γ-H2AX were detected. Moreover, DNA HR repair in terms of Rad51 declined when the cells were exposed to both radon and sodium arsenite. The synergistic effect of radon and sodium arsenite in HBE cells may be attributed to the enhanced DSBs and inhibited HR pathway upon co-exposure.