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Fascin is an actin-bundling protein and induces membrane protrusions and cell motility after the formation of lamellipodia or filopodia. Fascin expression has been reported to be associated with progression or prognosis in various neoplasms, but the role of fascin in hepatocellular carcinoma (HCC) remains unknown. The aim of this study was to investigate the clinicopathological and prognostic relevance of fascin by immunohistochemistry.A total of 137 patients with HCC were stained with anti-fascin antibody. The tumor cells having unequivocal cytoplasmic and/or membranous fascin immunoreactivity were defined as fascin-positive.Immunohistochemically, 23 (16.8%) HCCs having unequivocal fascin immunoreactivity were found. Tumors showing fascin expression were larger and less differentiated than those showing no fascin expression (P=0.0239 and 0.0018, respectively). Portal venous invasion, bile duct invasion, and intrahepatic metastasis were detected significantly more frequently in fascin-positive group (P=0.0029, 0.0333, and 0.0403, respectively). In addition, high alpha-fetoprotein (AFP) levels were significantly associated with the fascin expression in HCC (P=0.0116). Fascin-positive group had significantly poorer outcomes than fascin-negative group and was an independent prognostic factor for disease-free survival.Fascin might become a novel marker of progression in HCC and a significant indicator of a poor prognosis for patients with HCC.