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In the last decades, the use of in vitro systems in liver research has grown exponentially. Important reasons promoting this work are the high throughput and ease of genetic manipulations afforded by these experiments relative to in vivo experiments. Thousands of investigations of hepatocellular carcinoma have been performed employing the human hepatoma Huh-7 cell line. The extensive body of knowledge produced attests to the importance and value of this in vitro cell system to study the characteristics of hepatomas and the potential of natural and synthetic compounds to prevent and eliminate this liver cancer. The necessarily brief summary provided here attempts to summarise some of the most recent achievements and limitations of investigations with Huh-7 cells and derivatives.