Solid tumor cells may adapt to an ischemic microenvironment by upregulation of sodium/glucose cotransport (SGLT) across the plasma membrane which supplies the tumor cell with glucose even at very low extracellular glucose concentration. Since SGLT activity has been shown to depend on the epithelial growth factor receptor (EGFR) and EGFR reportedly is activated by ionizing irradiation, we tested for irradiation-induced SGLT activity.To this end, A549 cells were irradiated with 0 and 4 Gy X-ray and membrane potential was recorded by patch-clamp current-clamp mode in the presence and absence of extracellular glucose (5 mM), the SGLT inhibitor phlorizin (500 mM), and the inhibitor of the EGFR tyrosin kinase activity erlotinib (1 mM). In addition, the effect of SGLT blockage with phlorizin on the clonogenic survival of irradiated and control cells was tested by colony formation assays. As a result, irradiated cells exhibited a significantly lower membrane potential (-39 ± 2 mV, n = 22) than the control cells (-48 ± 2 mV, n = 39) 4 h after irradiation. Extracellular glucose removal (-22 ± 5 mV vs. -6 ± 2 mV, n = 7), phlorizin (-25 ± 2 mV vs. -15 ± 3 mV, n = 8–20), or erlotinib (-25 ± 2 mV vs. -11 ± 2 mV, n = 7–12) reversibly hyperpolarized the irradiated cells to a significantly higher extent than the control cells. In addition, phlorizin radiosensitized the A549 cells as evident from the colony formation assays. Taken together, these data suggest that irradiation stimulates an EGFR-mediated increase in the SGLT-generated glucose uptake which is required for the clonogenic survival of lung adenocarcinoma cells under genotoxic stress.