Less than 20% of hepatocellular carcinoma (HCC) develops in the non-cirrhotic liver (NCL). The diagnosis of HCC in NCL is suggested by a large hypervascular tumor in a 60–75 year old patient (usually male), particularly if the alpha-fetoprotein (AFP) level is high. But AFP is normal more often than not. Surgical resection is the only curative therapy of HCC; resection is more commonly feasible in HCC in NCL due to the healthy parenchyma of the underlying liver. The prognosis of HCC in NCL is better than that for HCC on cirrhosis with a 5-year survival approaching 50%. Prognosis is best in the patient with a small HCC with no vascular invasion or satellite nodules for whom an R0 resection can be achieved without the need for intra-operative transfusion. While intra-hepatic recurrence occurs frequently, it should be aggressively sought and treated; there is a major role for repeat hepatic resection and a lesser role for hepatic transplantation where results are poorer than those obtained for HCC on cirrhosis.