Background and Aims Immunotherapy is emerging as a new systemic treatment method for patients with hepatocellular carcinoma (HCC), with its clinically recognized therapeutic effects. However, imaging evaluation methods for assessing treatment response are still being explored. Imaging assessment is crucial in providing sufficient evidence for determining the primary clinical endpoints of immunotherapy in clinical practice. This study analyzes and compares the efficacy evaluation of immunotherapy in HCC using the Immune-Related Response Evaluation Criteria in Solid Tumors (iRECIST) and the modified Response Evaluation Criteria in Solid Tumors (mRECIST), aims to find a more suitable imaging assessment method for immunotherapy efficacy in HCC and facilitate the development of individualized and precise treatment plans by clinical physicians.Methods A retrospective analysis of clinical data from HCC patients who received PD-L1 monoclonal antibody immunotherapy at the First Affiliated Hospital of the Army Medical University from 2017 to 2021 was conducted. Of the patients, 58 were males, and 9 were females. Clinical imaging data from CT or MRI dynamic contrast-enhanced scans were collected at three time points: one week before treatment and two and four months after treatment initiation. The efficacy evaluations were performed using both iRECIST and mRECIST criteria, and the differences in the evaluation results between the two criteria were compared.Results Evaluation of immunotherapy efficacy using iRECIST and mRECIST criteria two and four months after PD-L1 monoclonal antibody treatment showed statistically significant differences (P<0.01). The main discrepancy between the two evaluation methods was observed in the objective response rate (ORR), with mRECIST showing a significantly higher ORR compared to iRECIST (P<0.01). Many patients who were classified as achieving complete or partial response using mRECIST were categorized as stable diseases according to iRECIST. Both evaluation methods indicated that approximately 50% of patients initially classified as progressive disease continued treatment and achieved stable or partial response status.Conclusion The mRECIST criteria, which measure "viable tumor" while excluding necrotic areas, provide a more objective and scientific approach to evaluate treatment efficacy. This approach prevents underestimation of treatment effects caused by significant tumor burden reduction despite minor changes in tumor size. On the other hand, iRECIST criteria propose concepts of unconfirmed and confirmed disease progression, making them more suitable for unique responses observed during immunotherapy, such as pseudo-progression. Therefore, it is recommended to adopt the mRECIST criteria for assessing "viable tumor" while considering the cyclic reevaluation model of iRECIST criteria to reassess patients initially classified as a progressive disease under mRECIST after the next treatment cycle to avoid premature treatment termination and potentially provide more clinical benefits to patients, as well as to offer guidance for clinicians to make subsequent treatment plans.