Background: Concurrent radiotherapy and chemotherapy represent the core treatment for nasopharyngeal carcinoma; however, the damage caused by this treatment can seriously affect patients’ immune function and quality of life. These effects may lead to treatment interruption, ultimately impacting treatment effectiveness. Methods: This retrospective study analyzed the role of thymosin as an immunomodulatory therapy in improving the immune function and quality of life in patients with nasopharyngeal carcinoma undergoing concurrent radiotherapy and chemotherapy between January and December 2023. Among 26 patients (15 men and 11 women, median age 53 years), the pathological type was non-keratinizing squamous cell carcinoma, undifferentiated, with staging ranging from T2N1 to T3N0M0 (stage II–III). All patients underwent concurrent chemoradiotherapy. Among them, 13 patients (the experimental group) received Thymosin therapy during the period of radiotherapy and chemotherapy and within 1 months after the end of treatment. Simultaneously, 13 patients (the control group) were matched and only received concurrent radiotherapy and chemotherapy. The radiation-induced oral mucositis, CD4+ T cell, CD8+ T cell, neutrophil count/lymphocyte count (NLR), lactate dehydrogenase (LDH), Epstein-Barr virus (EBV) DNA, and quality of life (QOL) of these patients was compared between the adjuvant treatment groups before, during, and 1 and 3 months after treatment. Results: At baseline, sex, age, pathological type, stage, CD4+, CD8+, NLR, LDH, EBV DNA, and quality of life scores did not differ significantly between the two groups before treatment. In the experimental group, during the same period of radiotherapy and chemotherapy, 13 patients with radiation-induced oral mucositis were mainly grade 1–2, and only 2 patients developed grade 3. However, all 13 patients in the control group developed grade 3–4 radiation-induced oral mucositis, which was considerably more severe than that in the experimental group. After 1 and 3 months of treatment, the CD4+ and CD8+ T cell counts were markedly higher in patients in the experimental group than those in the control group. Additionally, the experimental group also showed larger decreases in NLR, LDH, and EBV DNA compared with the control group. Moreover, the recovery of quality of life in the experimental group was significantly better than that in the control group (P<0.05). Conclusion: These results demonstrated that Thymosin neoadjuvant immunotherapy can improve the adverse side effects of concurrent radiotherapy and chemotherapy and enhance immune function and quality of life of patients with nasopharyngeal carcinoma.