The assessment of response to radiation-based therapies can be complicated by persistent or changing imaging features, and this field of study is still in active development even though imaging-based response assessment systems have been validated for the evaluation of response to ablative locoregional therapies. Research is still needed to address the shortcomings of current imaging criteria for evaluating tumor response to these novel techniques, despite the increased application of radiation-based local-regional therapies for the treatment of HCC following technological advancements and a better understanding of tumor biology.