Poly (ADP-ribose) polymerase (PARP) recognizes single- and double-strand DNA breaks and generates specific signals to facilitate DNA repair. In a genome-wide screening, we identified PARP-1 as a potential target for radiosensitization. PARP-1 is involved in the cellular response to DNA damage, and inhibiting its function can affect the repair process. Additionally, PARP-2, another member of the PARP family, also contributes to DNA repair and affects radiosensitivity. When both PARP-1 and PARP-2 are functionally inhibited, cells become more sensitive to ionizing radiation. In this study, we utilized several clinically approved PARP inhibitors to explore their effects on the radiosensitization in cancer cells. The combined impacts of γ-irradiation and PARP inhibitors on clonogenic cell survival, signal transduction, and cellular senescence were analyzed in cancer cells. We found that most of the PARP inhibitors showed radiosensitization effects on lung adenocarcinoma A549 cells. Rucaparib showed the highest enhancement ratio. Talazoparib showed radiosensitization at the lowest concentration. As a result of a combination of talazoparib and γ-irradiation, we observed an increased level of cellular senescence, accompanied by a decrease in the mitochondrial membrane potential. Our study provides insights into potential therapeutic strategies for enhancing cancer cell sensitivity to radiation. The effect of PARP inhibitors in combination with γ-irradiation on different types of cancer cell lines will also be discussed.