Objective To investigate the radiosensitizing effect of epigallocatechin gallate (EGCG) on radioresistant nasopharyngeal carcinoma (NPC) cells (C666-1R) in vitro and to preliminarily analyze the the related mechanisms. Methods Human NPC parental cells C666-1 and radioresistant cells C666-1R were cultured in vitro. The radioresistant phenotype of C666-1R was verified by cell morphology observation and proliferation assay after radiotherapy. The optimal working concentration of EGCG was screened by cell counting Kit-8 (CCK-8) assay. The C666-1R cells were divided into control group, radiotherapy group and radiotherapy combined with EGCG group. Cell proliferation ability was detected by CCK-8 assay, and cell apoptosis was detected by flow cytometry. The expression levels of proliferation-related molecules Cyclin D1 and Ki-67 and apoptosis-related molecules Bax and Bcl-2 were detected by real-time fluorescence quantitative polymerase chain reaction (qPCR) and Western blot. The mRNA expression of key genes (RAD51, PRKDC and XRCC5) in DNA damage repair was detected by RT-qPCR. Results Morphological and functional experiments indicated that C666-1R cells showed a significant radioresistant phenotype compared with C666-1 cells, and the inhibitory effect on proliferation after radiotherapy was significantly weakened. EGCG had a dose-dependent inhibitory effect on the proliferation of C666-1R cells, and 150 μg/mL was determined as the working concentration for subsequent combined radiotherapy after pre-experiment screening. Compared with the radiotherapy group, the proliferation rate of the radiotherapy combined with EGCG group was significantly decreased (P<0.05), and the apoptosis rate was significantly increased (P<0.05); the expressions of Cyclin D1 and Ki-67 were significantly down-regulated, the expression of Bax was up-regulated, and the expression of Bcl-2 was down-regulated (all P<0.05); the mRNA levels of RAD51, PRKDC and XRCC5 were significantly down-regulated (P<0.05), suggesting that it might be related to the affected process of DNA damage repair. Conclusions EGCG can significantly enhance the radiosensitivity of radioresistant NPC C666-1R cells in vitro. The mechanism may be related to the inhibition of cell proliferation, promotion of cell apoptosis and down-regulation of the expression of genes related to DNA damage repair. The upstream regulatory pathways and changes in DNA repair functions still need further research and verification.