Abstract Objectives The objective was to perform ex vivo evaluation of non-Gaussian diffusion kurtosis imaging (DKI) for assessment of hepatocellular carcinoma (HCC), including presence of treatment-related necrosis, using fresh liver explants. Methods Twelve liver explants underwent 1.5-T magnetic resonance imaging using a DKI sequence with maximal b-value of 2000 s/mm2. A standard monoexponential fit was used to calculate apparent diffusion coefficient (ADC), and a non-Gaussian kurtosis fit was used to calculate K, a measure of excess kurtosis of diffusion, and D, a corrected diffusion coefficient accounting for this non-Gaussian behavior. The mean value of these parameters was measured for 16 HCCs based upon histologic findings. For each metric, HCC-to-liver contrast was calculated, and coefficient of variation (CV) was computed for voxels within the lesion as an indicator of heterogeneity. A single hepatopathologist determined HCC necrosis and cellularity. Results The 16 HCCs demonstrated intermediate-to-substantial excess diffusional kurtosis, and mean corrected diffusion coefficient D was 23% greater than mean ADC (P=.002). HCC-to-liver contrast and CV of HCC were greater for K than ADC or D, although these differences were significant only for CV of HCCs (P≤.046). ADC, D and K all showed significant differences between non-, partially and completely necrotic HCCs (P≤.004). Among seven nonnecrotic HCCs, cellularity showed a strong inverse correlation with ADC (r=−0.80), a weaker inverse correlation with D (−0.24) and a direct correlation with K (r=0.48). Conclusions We observed non-Gaussian diffusion behavior for HCCs ex vivo; this DKI model may have added value in HCC characterization in comparison with a standard monoexponential model of diffusion-weighted imaging.