Hepatocellular carcinoma (HCC) is the third most common cause of cancer-related mortality worldwide. We have previously reported that LASP-1 is a downstream protein of the urokinase type plasminogen activator (uPA). Here we investigated the role of LASP-1 in HCC by a molecular and biological characterization of LASP-1 expression in human HCC specimens and in cultured HCC cells. We determined the LASP-1 mRNA expression levels in 55 HCC cases with different hepatic background disease. We identified 3 groups of patients with high, equal or low LASP-1 mRNA levels in HCC tissues compared to the peritumoral (PT) tissues. In particular we found that i) the HCCs displayed a higher LASP-1 mRNA level in HCC compared to PT tissues; ii) the expression levels of LASP-1 mRNA in female HCCs were significantly higher compared to male HCCs; iii) the cirrhotic HCCs displayed a higher LASP-1 mRNA. Further, the biological characterization of the ectopic LASP-1 overexpression in HCC cells, using MALDI-TOF mass spectrometer on the LASP-1 co-immunoprecipitated fractions, displayed vimentin as a novel putative partner of LASP-1. Our results suggest that LASP-1 mRNA overexpression may be mainly implicated in female HCCs and cirrhotic HCCs; and that LASP1 may play its role with vimentin in HCC cells.