The aim of the study was to prospectively evaluate the clinical value of intravoxel incoherent motion (IVIM)-magnetic resonance imaging (MRI) in early predicting the treatment response to neoadjuvant chemotherapy (NAC) for nasopharyngeal carcinoma (NPC). Forty-eight patients with locoregionally advanced NPC were imaged with IVIM-MRI (14 b-factors, 0-1000 s/mm2) on a 3.0-T Magnetic resonance system, at the baseline, and repeatedly at the third and 21st day after NAC started. The IVIM-derived parameters (D*, pure diffusion coefficient; f, perfusion fraction; and D, pseudodiffusion coefficient) were calculated with the Interactive Data Language version 6.3 software. The baseline parameters and their corresponding changes (Δparameter(day)) during NAC were compared using the Student t test or Mann-Whitney U test. Variation analyses of IVIM-derived parameters were tested with intraclass correlation coefficient. Receiver-operating characteristic (ROC) curve analysis was conducted to estimate the best diagnostic accuracy. Statistical analyses were performed on the SPSS 18.0 software, with a 2-tailed probability value, P < 0.05 was considered significant. Among recruited patients, 37 cases were categorized as responders and 11 cases as nonresponders after NAC completed. The intra- and interobserver intraclass correlation coefficient of IVIM-derived parameters were excellent, which ranged from 0.858 to 0.971. Compared with the baseline value, at the third and 21st day, the D value was significantly higher and the D* value significantly lower (P < 0.05, P < 0.001, respectively). In contrast, f parameter only changed slightly (P > 0.05). Compared with nonresponders, responders presented a notably lower baseline D value and higher ΔD3, ΔD21, ΔD3*, ΔD21*, and Δf21 (P < 0.05), but no significant change in Δf3 was observed (P > 0.1). The receiver-operating characteristic curve analyses indicated that the threshold of baseline D values that best predicted the responders for primary nasopharynx tumors and metastatic lymph nodes were 0.911 × 10(-3) mm2/s versus 0.951 × 10(-3) mm2/s, and their corresponding area under curve, sensitivity, and specificity were 0.714 versus 0.774, 0.658 versus 0.538, and 0.818 versus 0.944, respectively. IVIM-MRI can potentially early predict the treatment response of NAC for NPC patients. The baseline D value, and early changes in D and D value are better predictors of the chemotherapeutic responsiveness.