Hepatocellular carcinoma (HCC) is an important cancer worldwide. The main curative treatment modality is surgical resection although only a minority of afflicted patients are amendable because of poor liver function reserve or extensive disease at the time of diagnosis. The selection criteria for surgical resection, however, are variable and frequently appear to be center-specific. Further, they are influenced by rapidly evolving data on the outcomes of surgical resection and other emerging modalities of treatment. Recently, two major international practice guidelines on the management of HCC were published at about the same time, namely those of the American Association for the Study of the Liver (AASLD), and of the Asia-Pacific Association for the Study of the Liver (APASL). These two practice guidelines differ significantly in philosophy and practice with regards to surgical resection. In fact, they reflect the two extremes of a spectrum of existing consensus opinions. The AASLD Guidelines have evolved from the guidelines of the Barcelona Clinic for Liver Cancer (BCLC), and are significantly more conservative with regard to surgical resection compared with the APASL Guidelines. The scientific basis for these major differences in criteria with regard to surgical resection for HCC is reviewed here, particularly with regard to the situation in the Asia-Pacific region where HCC is especially common.