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Objective: To investigate whether pre-treatment and middle-treatment plasma Epstein–Barr virus (EBV) DNA loads are useful predictors of prognosis and indicators of therapy modification in nasopharyngeal carcinoma (NPC) patients undergoing radical concurrent chemoradiotherapy (CCRT). Methods: Plasma EBV DNA load was measured by quantitative polymerase chain reaction before treatment (pre-DNA) and during the second cycle of DDP (mid-DNA). The primary endpoint was 5-year progression-free survival (PFS). Results: A total of 775 NPC patients treated with CCRT were included. In total, 553 patients with pre-DNA 200 mg/m 2 cumulative cisplatin dose (CCD) but were associated with fewer all-grade late toxicities. However, in the high-risk group (pre-DNA ⩾4000 copies/mL or detectable mid-DNA), patients receiving >200 mg/m 2 CCD showed a higher 5-year PFS (73.1% versus 58.6%, p = 0.027) and locoregional relapse-free survival (88.5% versus 76.1%, p = 0.028) than those receiving ⩽200 mg/m 2 CCD. Conclusion: The combination of pre-DNA and mid-DNA could be particularly useful for guiding risk stratification and early treatment modification for NPC treated with CCRT. A total of 200 mg/m 2 cisplatin seemed to be the optimal dose for the low-risk patients, while >200 mg/m 2 cisplatin may be adequate to achieve satisfactory survival outcomes in the high-risk group.