Dietary intake of the natural omega-3 fatty acid docosahexaenoic acid (DHA) has been implicated in protecting patients with viral hepatitis B or C from developing hepatocellular carcinoma (HCC). Little is known about the effects of DHA on established solid tumors. Here we describe a low-density lipoprotein−based nanoparticle that acts as a transporter for unesterified DHA (LDL−DHA) and demonstrates selective cytotoxicity toward HCC cells. We investigated the ability of LDL−DHA to reduce growth of orthotopic hepatomas in rats.