Purpose: To evaluate the prognostic value of magnetic resonance imaging (MRI)-detected tumor residue after intensity-modulated radiation therapy (IMRT) and its association with post-treatment plasma Epstein-Barr virus deoxyribonucleic acid (EBV DNA) in nasopharyngeal carcinoma (NPC). Methods and materials: A prospective database of patients with histologically-proven NPC was used to retrospectively analyze 664 cases. Pre-and post-treatment MRI scans were independently reviewed by two senior radiologists who were blinded to clinical findings. Factors significantly associated with MRI-detected tumor residue were identified and included in the following multivariate logistic regression model. Residual risk model were established. Receiver operating characteristic (ROC) identify the optimal cut-off risk score for tumor residue. Results: MRI-detected residual tumor at three months after IMRT was associated with poor prognosis. The 5-year survival rates for the non-residual and residual groups were: OS (93.8% vs. 76.6%, P<0.001), PFS (84.7% vs. 67.9%, P=0.006), LRFS (93.4% vs. 80.4%, P=0.002), and DMFS (90.3% vs. 87.9%, P=0.305), respectively. Three-month post-treatment EBV DNA was significantly associated with tumor residue (P<0.001). A residual risk score model was established, consisting of T and N categories and post-treatment EBV DNA. ROC identified 22.74 as the optimal cut-off risk score for tumor residue. High-risk score was independently associated with poor treatment outcomes. Conclusions: MRI-detected tumor residue was an independent adverse prognostic factor in NPC; and significantly associated with three-month post-treatment EBV DNA. As limited resources in some endemic areas prevent patients from undergoing routine post-treatment imaging, our study identifies a selection risk-model, providing a cost-effective reference for the selection of follow-up strategies and clinical decision-making.