〔Abstract〕 Objective To investigate the effect of Brigatinib on radiation sensitivity of colorectal cancer LOVO cells by treating colorectal cancer LOVO cells with a combination of radiation and brigatinib. Methods Western blot and immunofluorescence detection were used to detect the amount of epidermal growth factor receptor(EGFR), p-EGFR expression in colorectal cancer cells after treatment with different irradiation doses. The expression levels of EGFR, p-EGFR, γ-H2 AX, cleaved caspase-3, cleaved caspase-7 and cleaved caspase-9 in LOVO cells were determined by Western blot, the levels of Non-homologous End Joining-NHEJ were detected by DR-GFP plasmid system, cell viability was detected by CCK-8 and apoptosis was detected by annexinv FITC/PI double labeling. Results Radiation treatment significantly increased EGFR phosphorylation in LOVO cells, which was inhibited in a dose-dependent manner after treatment with Brigatinib. Non-homologous End Joining repair was inhibited following Brigatinib treatment, and a significant increase in apoptosis was observed in LOVO cells treated with combined Brigatinib and radiation. Conclusion Brigatinib inhibited non homologous end joining repair and promoted apoptosis in LOVO cells by inhibiting EGFR phosphorylation, which eventually increased the radiation sensitivity of LOVO cells.