Despite surgical resection being a curative mainstay for the treatment of hepatocellular carcinoma (HCC) with 5-year overall survival rates approaching 60% less than 50% of newly diagnosed HCC patients are candidates for resection. The decision process to undergo surgical resection should take into account both patient- and tumor-related factors and discussed in a multidisciplinary approach. Although tumor size is associated with multifocality and presence of macrovascular invasion, in the absence of those two factors, large tumor size should not be a contraindication for surgical resection. However, the presence of multifocal HCC tumors or associated macrovascular invasion is a relative contraindication and surgical resection should be offered on a case-by-case basis after consideration of other treatment modalities. Careful assessment of patient-related factors including portal hypertension, underlying liver dysfunction, and functional liver remnant is crucial to reduce perioperative complications ensuring safe surgical resection.