Even if there are no definitive evidence that hepatocellular carcinoma (HCC) screening in high-risk groups improves survival, many physicians screen high-risk population by various strategies, alpha-fetoprotein (AFP) and liver ultrasonography are the most widely used tools. AFP sensitivity and specificity depend on the cut-off value chosen. In cirrhotic patients, using a cut-off level of 20 ng/mL, sensitivity is only around 60% and positive predictive value ranges from 9% to 50%, depending on HCC prevalence. Sensitivity and specificity are much higher (94.1% and 99.9%, respectively) in hepatitis B carriers, but positive predictive value is only 5%. The performance of ultrasonography as a screening tool varies widely depending on the experience of the examiner and the technology used. Recent studies generally indicate a 60% sensitivity or higher, a specificity greater than 90%, and a positive predictive value of 70%. Based on the estimated HCC doubling time, the recommended screening interval is 6 months, although a 1 year interval seems as effective. Currently, HCC screening with AFP only is not recommended except when ultrasonography is either not available or of poor quality. Ultrasonography seems more efficient as a screening tool. Pathology assessment of liver explants in living donor transplantation programs will provide more precise and reliable information regarding the value of AFP and ultrasonography as HCC screening tools.