This study aimed to evaluate the synergistic effect of propolis extract-zinc oxide (EEP-ZnO) nanocomposite against human lung carcinoma cell line. EEP-ZnO nanocomposite was formulated by the combination of Zinc Oxide nanoparticles (ZnO NPs) with ethanolic propolis extract (EEP) that was characterized by X-ray diffraction (XRD), Transmission electron microscopy (TEM) and Fourier transform infrared spectroscopy (FT-IR). The MTT assay and Annexin V-PI apoptosis assay were used for cytotoxicity evaluation of prepared EEP-ZnO nanocomposite against human lung carcinoma cell line (A549) and human lung normal cell line (WI-38). Results showed that the propolis extract- zinc oxide nanocomposite significantly decreased cell viability and increased cell apoptosis, as compared to EEP and ZnO NPs alone. It was also observed that EEP, ZnO NPs, and EEP-ZnO nanocomposite are exhibited a less toxic effect on WI-38 comparable to A549.