Background Hepatocellular carcinoma (HCC) is one of the most common causes of cancer-related deaths worldwide in both men and women. Early-stage HCCs are treated either by curative surgical resection and/or by locoregional interventions, such as radiofrequency ablation or trans-arterial chemoembolization. Functional imaging as diffusion-weighted magnetic resonance imaging (DW MRI) and metabolic imaging with 18F-positron emission tomography/computed tomography (18F-FDG PET/CT) has been used for assessment of treatment response. This retrospective study was conducted on 29 patients known to have HCC with locoregional therapeutic interventions and referred for radiological follow-up searching for residual/recurrence neoplasia or metastatic deposits. The study aimed to assess the benefits of using the metabolic parameters of 18F-FDG PET/CT in the follow-up of HCC patients after therapeutic interventions in comparison with DW MRI. Results Regarding qualitative assessment of residual active viable HCC by PET/CT and DW MRI, the sensitivity, specificity, PPV, NPP and accuracy were 77.3%, 91.7%, 94.4%, 68.8%, 82.4% and 95.5%, 75%, 87.5%, 90%, 88.2%, respectively. The optimal cutoff point of the SUVmax to differentiate viable from non-viable HCC was 3.4 (AUC = 0.898), with sensitivity, specificity, PPV and NPV of 77.27%, 100.0%, 100.0% and 66.7%, respectively. The optimal ADC cutoff value for discrimination between viable and non-viable HCC was 1247 mm2/s (AUC = 0.976) with sensitivity, specificity, PPV and NPV of 90.48%, 100.0%, 100.0% and 83.3%, respectively. New hepatic lesions were found in 38.2% of patients by DW MRI, while detected only in 26.5% of patients by PET/CT. The PET/CT revealed extrahepatic metastasis in 44.1% of patients, while detected only in 8.8% of patients by DW MRI. Conclusions DWI was more sensitive than PET/CT for detecting tumor residual and hepatic recurrence compared to PET/CT which was much better in detecting distant metastases.