The radiosensitizing effects of MEK inhibitor U0126 on A549 cells were determined by colony forming assay. A549 cells were exposed to X-ray with or without U0126 treatment. MTT assay was used to evaluate the cell viability. Cell cycle distribution was analyzed by flow cytometry. Expression of p-erk protein was confirmed by Western Blot. SA-β-gal assay was used to measure the phenomenon of senescence. The results showed that U0126 could decrease the expression of p-erk protein while enhance the radiosensitivity of A549 cells, and the SER was 1.18. ERK inhibition significantly suppressed cell viability and induced G1-phase arrest. After treatment of U0126 combined with X-ray irradiation, the phenomenon of G1-phase arrest and senescence appeared more obvious. U0126 can enhance the radiosensitivity of A549 cells. The radiosensitizing effects of U0126 on A549 cells may contribute to the increase in phenomenon of G1-phase arrest and senescence.Cited