Background: Although immune checkpoint inhibitor (ICI) therapy has revolutionized the treatment of nasopharyngeal carcinoma (NPC), it is still the second-or third-line treatment after the failure of radiotherapy or chemotherapy. In this study, we aimed to investigate the impact of concurrent chemoradiotherapy (CCRT) on programmed death-ligand 1 (PD-L1) protein expression in NPC patients. Methods: We enrolled 24 NPC patients treated with intensity-modulated radiation therapy (IMRT) combined with cisplatin CCRT. PD-L1 expression was evaluated by immunohistochemistry, and next generation sequencing and annotation were performed to determine the genetic alteration after CCRT. Results: Our results showed that patients with a high expression of PD-L1 were more inclined to a complete response (CR) to chemoradiotherapy, as opposed to a partial response (PR) (P<0.05). Moreover, the mean values of the tumor mutation burden (TMB) and the tumor neoantigen burden (TNB) in the PD L1 positive group were significantly lower than that of the PD-L1 negative group in our cohort. Conclusions: We confirmed that the TMB and TNB may be potential clinical indicators in NPC treatment, and PD-L1 expression may be a clinical biomarker in NPC chemoradiotherapy. Finally, through next-generation sequencing and annotation, we found that the most frequent driver gene mutations in NPC were TET2, TP53, and MAPK.