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Hepatocellular carcinoma (HCC) has long been one of the most important causes of cancer mortality in the world. Many natural products and traditional herbal medicines have been used to treat HCC in Asian countries such as Japan, Korea, Taiwan, and China. The present review aims to describe the anticancer properties and apoptotic mechanisms of cinnamaldehyde, the bioactive ingredient isolated from cinnamon trees, and the herbal prescription Huang-Lian-Jie-Du-Tang (黃連解毒湯 Huáng Lián Jiě Dú Tang; HLJDT) against human hepatoma cells in vitro and in vivo. Implication of their treatment for the development of targeted therapy against HCC is discussed.