Background and study aim: Hepatocellualr carcinoma (HCC) is an increasing problem in Egypt. Clusterin has been reported to play a significant role in tumorigenesis. The aim of this study is to evaluate clusterin as a marker for evaluating diagnosis and metastasis potential of HCC. Patients and Methods: Eighty patients with HCC, 30 patients with liver cirrhosis, 30 patients with chronic hepatitis and 30 healthy controls were enrolled in study. The diagnosis of HCC patients was based on computed tomography. Estimation of serum clusterin was done by enzyme linked immunosorbent assay. Results: Serum clusterin levels were significantly increased in patients with HCC (P<0.001). Serum clusterin reached the lowest significant levels in cirrhotic patients. Serum clusterin was highly increased in patients with poorly differentiated tumor and in those with capsular infiltration; also it was significantly related with portal vein invasion and lymph node infiltration. In addition, serum clusterin levels were significantly increased according to the progression of Barcelona Clinic Liver Cancer and Tumor-Nodes-Metastasis staging systems. However, these findings were not observed with alpha fetoprotein (AFP). Receiver operator characteristic curve showed that clusterin had a greater area under curve value (0.95) than that of AFP (0.85). At cutoff value 128 ug/ml, serum clusterin yielded 90% sensitivity and 87% specificity for predicting HCC. While at cutoff value 100 ng/ml, serum AFP had 75% sensitivity and 80% specificity. Conclusion: We concluded that serum clusterin is a promising useful marker for diagnosis of HCC. Higher level of clusterin was closely related to capsular infiltration, venous invasion, lymph node metastasis and poorly differentiated tumor suggesting that clusterin might be deemed as a useful marker for predicting the progression and metastasis potential of HCC.