The objective of this study is to investigate the possible transmission mechanism of inter-flat air cross-contamination under the condition of singlesided natural ventilation. In high-rise residential building with flush windows on the same side, the air pollutants can diffuse from lower flat to adjacent upper flat in the vertical direction related to the interflat air flow through open windows caused by the temperature difference between the indoor air and the air outside of the windows. Based on the validation of CFD models with experimental data given by Heiselberg, the renormalization group (RNG) based k −ε model, together with Carbon dioxide (CO2) used as a tracer, is chosen to reveal this air crosscontamination. Different effects of contamination spread into upper room were evaluated through kinds of cases performed in various conditions. The numerical results demonstrate this possible transmission path.