Hepatocellular carcinoma (HCC) is the fifth most common malignancy worldwide. There is a substantial need for new chemotherapeutic drugs effective against this tumor. Doxorubicin (DOXO), used for chemoembolization of HCCs, is poorly efficacious when administered systemically at conventional doses; dose escalation is hindered by unacceptable toxicity. Here, we review preclinical experiments showing that the efficacy of DOXO against HCCs and its safety increased following conjugation to lactosaminated human albumin (L-HSA). L-HSA-DOXO was initially prepared to improve the anticancer activity of the drug on well-differentiated HCCs, which actively internalize L-HSA by means of the asialoglycoprotein receptor. Unexpectedly, it was found that the conjugate enhanced DOXO concentrations in all forms of HCCs, independently of their differentiation grade.