The most important and primary endpoint in oncology research is overall survival. However, other endpoints such as time-to-progression, time-to-recurrence and response rate have their roles in oncology trials and these endpoints are assessed by the imaging evaluation of tumor burden. Recently published the revised version (version 1.1) of response evaluation criteria in solid tumors (RECIST) is now the standards for the tumor response evaluation after treatment, and especially for cytotoxic agents. However, the problems are more complicated for hepatocellular carcinoma (HCC). RECIST are mainly used for the response evaluation of chemotherapeutic agents. However, for the treatment of HCC, there are some locoregional treatments and molecular targeted agents, and after these treatments, tumor necrosis remains as non-enhanced tumor areas, whereas viable tumor parts can be noted by the enhanced areas. However, these necrotic areas should be included as being tumor when we adopt the pure anatomical criteria such as RECIST and this can distort the results of the response evaluation. For overcoming this problem, some new criteria were introduced and their principle is the measurement of enhancing portion of the tumor only. However, these new criteria still have limitations and functional imaging is thought to be the future problem-solving tool for the evaluation of response for molecular targeted agents.