To investigate the correlation between tumor volume reduction rate (TVRR) and prognosis in patients with diverse clinical types of nasopharyngeal carcinoma (NPC) undergoing chemoradiotherapy, thereby aptly categorizing risks and directing the personalized treatment of NPC.A total of 605 NPC patients with varying clinical types were enrolled in this study and subsequently segregated into six subgroups based on their clinical types and TVRR. To accentuate the efficacy of grouping, Groups 1-6 underwent clustered analysis of hazard atio (HR) values pertaining to progression-free survival (PFS), forming three risk clusters denoted as low, intermediate, and high. The log-rank test was employed to discern differences, and R 4.1.1 was utilized for cluster analysis.According to survival rates, we classified the first (G2 and G4), second (G1 and G6), and third (G3 and G5) risk clusters as low-, intermediate-, and high-risk, respectively. When comparing risk stratification with the 8th edition of the TNM staging system, our classification exhibited superior predictive prognostic performance. Subgroup analysis of treatments for each risk cluster revealed that the PFS in the neoadjuvant chemotherapy (NACT) + concurrent chemoradiotherapy (CCRT) group surpassed that of the CCRT group significantly (p < 0.05).The reliance on clinical types and TVRR facilitates risk stratification of NPC during chemoradiotherapy, providing a foundation for physicians to tailor therapeutic strategies. Moreover, the risk cluster delineated for NPC patients during the mid-term of chemoradiotherapy stands as an independent prognostic factor for progression-free survival (PFS), overall survival (OS), distantmetastasis-free survival (DMFS), and local recurrence-free (LRRFS) posttreatment. Additionally, individuals in the high-risk cluster are recommended to undergo adjuvant chemotherapy after CCRT.© 2024 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.