Objective To investigate the inhibitory effect of CL-387785 on the invasion and metastasis of EGFR T790M mutant H1975 cells and its sensitization of radiotherapy. Methods The H1975 cell was treated with 0，10， 25， 50， 100 nmol/L CL-387785. The MTT colorimetric assay was used to detect the proliferation inhibition rates at 24，48，72 and 96 h after treatment. Moreover，Annexin-FITC/PI double staining method via flow cytometry was used to detect the apoptotic rates of different concentrations of CL-387785 at 48 and 96 h. Changes of invasion and migration of H1975 cells treated with CL-387785 were detected by Transwell and scratch assay， respectively. The clone formation assay was employed to investigate the survival fraction（SF） of the H1975 cells after exposure to CL-387785 following different doses of X-ray （0， 2， 4， 6， 8 and 10 Gy） irradiation. The target model was fitted to the cell survival curve to calculate the sensitization enhancement ratio （SER）. Results CL-387785 inhibited the proliferation of H1975 cells， and dose- and time-dependently increased the inhibition rates of the proliferation in range of 10-100 nmol/L. CL-387785 could induce the apoptosis and decrease the number of penetrate-membrane cell and migration distance of H1975 cells in a dose-dependent manner （P＜0.05）. In the 2-10 Gy irradiation range， the SF of 10， 25， 50 and 100 nmol/L CL-387785 were lower than that of 0 nmol/L，and SF decreased with the increase of concentration of CL-387785 and above differences were statistically significant （P＜0.05）. Compared with the 0 nmol/L CL-387785， the SER of 25， 50， 10， 100 nmol/L CL-387785 SER after treatment were 1.17， 1.39， 2.88 and 3.64， respectively. Conclusion The irreversible EGFR inhibitor CL-387785 can inhibit the invasion and metastasis of T790M EGFR mutant H1975 cells and has the effect of radiation sensitization.