Physiological changes in tumour occur much earlier than morphological changes. They can potentially be used as biomarkers for therapeutic response prediction. This study aimed to investigate the optimal time for early therapeutic response prediction with multi-parametric magnetic resonance imaging (MRI) in patients with nasopharyngeal carcinoma (NPC) receiving concurrent chemo-radiotherapy (CCRT). Twenty-seven NPC patients were divided into the responder (N=23) and the poor-responder (N=4) groups by their primary tumour post-treatment shrinkages. Single-voxel proton MR spectroscopy (1H-MRS), diffusion-weighted (DW) and dynamic contrast-enhanced (DCE) MRI were scanned at baseline, weekly during CCRT and post-CCRT. The median choline peak in 1H-MRS, the median apparent diffusion coefficient (ADC) in DW-MRI, the median influx rate constant (Ktrans), reflux rate constant (Kep), volume of extravascular-extracellular space per unit volume (Ve), and initial area under the time-intensity curve for the first 60s (iAUC60) in DCE-MRI were compared between the two groups with the Mann-Whitney tests for any significant difference at different time points. In DW-MRI, the percentage increase in ADC from baseline to week-1 for the responders (median=11.39%, IQR=18.13%) was higher than the poor-responders (median=4.91%, IQR=7.86%) (p=0.027). In DCE-MRI, the iAUC60 on week-2 was found significantly higher in the poor-responders (median=0.398, IQR=0.051) than the responders (median=0.192, IQR=0.111) (p=0.012). No significant difference was found in median choline peaks in 1H-MRS at all time points. Early perfusion and diffusion changes occurred in primary tumours of NPC patients treated with CCRT. The DW-MRI on week-1 and the DCE-MRI on week-2 were the optimal time points for early therapeutic response prediction.