Natural compounds such as propolis have gained wide popularity in the last decades. While its antibacterial, antiviral, and antifungal properties are well known, the anticancer properties of propolis are just beginning to be appreciated. Herein, we comparatively investigate the cytotoxic and radiosensitizing potential of four different ethanolic propolis extracts originating from three different countries (Germany, Ireland, South Africa) in human lung cancer cell models. Liquid chromatography-mass spectrometry (LC-MS/MS) was applied to characterize the four different propolis extracts. Cytotoxicity and radiation survival were determined by 3D matrix-based clonogenic assays and autophagy was examined by western blotting. We found cytotoxicity in a propolis type-, time- and cell model- dependent manner. In the four ethanolic propolis extracts, Coumaric acid, Caffeic acid phenethyl ester, Pinocembrin and Chrysin presented the major compounds identified. Examining the induction of autophagy using the marker LC3B and autophagy inhibition with chloroquine suggested autophagy to be part of the survival mechanisms upon propolis treatment in a cell model-dependent manner. Combining propolis with X-ray irradiation showed the radiosensitizing potential of propolis in human lung cancer cell models, which clearly presented in a manner dependent on the incubation time of propolis and the cell model treated. Propolis treatment showed cytotoxic and radiosensitizing effects of propolis on human lung cancer cells. Since these effects differ greatly between the four propolis extracts studied and originating from different regions, further studies are urgently needed to differentiate propolis species and their anticancer properties in more detail.