The pathological differentiated grade is heavily associated with the hepatocellular carcinoma prognosis. Through a prospectively research, we sought to determine the diagnostic performances of three methods of ROI placement for measurements of IVIM parameters in the grading of hepatocellular carcinoma. According to the results, we found that different ROI positioning methods used significantly affects the IVIM and ADC parameters measurements. Measurements of ADCslow value derived from whole tumor volume method entailed the highest diagnostic performance in grading hepatocellular carcinoma. These results suggested that ADCslow value derived from whole tumor volume method might be useful in assessing the differentiated grade of carcinoma, and which might be helpful in predicting the patients’ prognosis.