Background: Epstein-Barr virus (EBV) DNA is a well-established biomarker in nasopharyngeal carcinoma (NPC), but its integration into artificial intelligence (AI)-based prognostic tools remains limited. This study aimed to develop and validate AI models incorporating EBV DNA load levels to predict progression-free survival (PFS) in patients with advanced NPC treated with concurrent chemoradiotherapy (CRT). Methods: A retrospective multicenter cohort of 503 patients was divided into training (n = 301) and validation (n = 202) sets. Four machine learning algorithms-Cox regression, LASSO, RSF, and GBM-were applied to predict 1- and 1.5-year PFS in patients with advanced NPC. Model performance was evaluated using the concordance index (C-index), time-dependent receiver operating characteristic (ROC), decision curve analysis (DCA), and interpretability tools such as SHAP values and partial dependence plots (PDP). Results: The 1-, 3-, and 5-year PFS rates were 100.0%, 91.5%, and 88.6% in the EBV = 0 group; 99.4%, 91.2%, and 88.5% in the > 0 and < 1500 group; and 92.3%, 81.0%, and 75.7% in the >= 1500 group, respectively, with statistically significant differences among the three groups (P = 0.0024). The RSF model outperformed other models with the highest C-index (0.778) and area under the ROC curve of 0.810 and 0.634 at 1 and 1.5 years, respectively. EBV DNA emerged as the most influential predictor across all interpretability analyses. Patients with EBV DNA >= 1500 copies/ml had the poorest predicted survival, showing a distinct threshold effect in the PDP. Conclusions: High EBV DNA levels were associated with poorer PFS in advanced NPC. Among the models evaluated, the RSF model demonstrated the best predictive performance and interpretability. EBV-informed AI modeling represents a promising approach for enhancing individualized risk prediction and clinical decision-making in NPC.