Primary liver cancer, also known as hepatocellular carcinoma (HCC), is one of the most lethal cancers having worldwide prevalence. Although most HCC cases are reported in the developing countries of Asia and Africa, there has been an alarming increase in HCC cases in Western Europe as well as United States. Chronic liver diseases, viral hepatitis, alcoholism as well as dietary carcinogens, such as aflatoxins and nitrosoamines, contribute to HCC. Liver transplantation as well as surgical resection at best offer limited treatment options. Thus, there exists a critical need to investigate and evaluate possible alternative chemopreventive and therapeutic strategies which may be effective in the control of liver cancer. HCC, most often, develops and progresses in a milieu of oxidative stress and inflammation. Phytochemicals, such as dietary polyphenols endowed with potent antioxidant as well as anti-inflammatory properties, provide a suitable alternative in affording alleviation of HCC. Curcumin, the principal polyphenolic curcuminoid, obtained from the turmeric rhizome Curcuma longa has long been used to cure several chronic ailments, such as neoplastic and neurodegenerative diseases. Studies suggest that curcumin may have antitumor, antioxidant, and anti-inflammatory properties. This article reviews the effects of curcumin in preclinical in vitro and in vivo models of HCC with particular emphasis to its antioxidant, apoptotic and anti-inflammatory effects as well as involvement in various molecular signaling mechanisms. This review also discusses potential challenges involved in the use of curcumin in HCC, such as bioavailability, pharmacokinetics, drug delivery as well as paucity of clinical studies.