AIM: To investigate whether intra-procedural diffusionweighted magnetic resonance imaging can predict response of hepatocellular carcinoma (HCC) during transcatheter arterial chemoembolization (TACE). METHODS: Sixteen patients (15 male), aged 59 ± 11 years (range: 42-81 years) underwent a total of 21 separate treatments for unresectable HCC in a hybrid magnetic resonance/interventional radiology suite. Anatomical imaging and diffusion-weighted imaging (b = 0, 500 s/mm2) were performed on a 1.5-T unit. Tumor enhancement and apparent diffusion coefficient (ADC, mm2/s) values were assessed immediately before and at 1 and 3 mo after TACE. We calculated the percent change (PC) in ADC values at all time points. We compared follow-up ADC values to baseline values using a paired t test (α = 0.05). RESULTS: The intra-procedural sensitivity, specificity, and positive and negative predictive values (%) for detecting a complete or partial 1-mo tumor response using ADC PC thresholds of ±5%, ±10%, and ±15% were 77,67, 91, and 40; 54, 67, 88, and 25; and 46, 100, 100,and 30, respectively. There was no clear predictive value for the 3-mo follow-up. Compared to baseline, the immediate post-procedure and 1-mo mean ADC values both increased; the latter obtaining statistical significance (1.48 ± 0.29 mm2/s vs 1.65 ± 0.35 × 10-3 mm2/s, P < 0.014). CONCLUSION: Intra-procedural ADC changes of > 15% predicted 1-mo anatomical HCC response with the greatest accuracy, and can provide valuable feedback at the time of TACE.