RecQL1 in the human RecQ DNA helicase family participates in DNA repair and recombination pathways in cell cycle replication. Immunohistochemical analysis of human hepatocellular carcinoma (HCC) tissues showed that RecQL1 expression is strongly correlated with histological grade and MIB-1 indices of HCC, and that the expression was greater in simple HCCs inducing extranodular growth or portal vein invasion than in HCCs not inducing extranodular growth or portal vein invasion. These histological data reveal the potential of RecQL1 as a biological marker predicting the malignancy and progression of liver cancer. High expression profiles were also produced by various HCC cells, including HCC cell lines established by us. When RecQL1 expression was silenced by siRNA in vitro, most HCC cells died of mitotic catastrophe. In a mouse orthotopic xenograft model of liver cancer with transplanted human HCC, RecQL1-siRNA mixed with cationic liposomes exhibited a strong anticancer effect that prevented the growth of the cancer. RecQL1-siRNA inhibited the growth of human HCC in the mouse liver, confirming that RecQL1 is an excellent molecular agent against liver cancer and suggests that RecQL1-siRNA formulated with liver-prone liposomes has excellent potential as a therapeutic drug against liver cancers.