Journal of clinical gastroenterology is part of the Juniper publishers which is devoted to publish subject-specific articles focused on the needs of individual research communities across all areas of biology and medicine. Hepatocellular carcinoma (HCC) is one of the most feared complications of liver disease due to its high mortality rate combined with lack of effective treatments, which at present are predominantly ablative and surgical. Current molecularly-targeted therapeutic treatments of HCC target common survival pathways of cancer cells and regenerating hepatocytes. Therefore, the combination treatment designed to eliminate drug-resistant tumor cells may be additionally toxic to hepatocytes. Since hepatocyte death promotes HCC, hepatotoxicity presents a challenge for successful HCC treatments. On the other hand, although cancer cell death reduces HCC burden, hepatocyte death exacerbates HCC development. Therefore, balancing hepatocyte death and cancer cell death is a key aim for successful HCC treatments. Consequently, small molecules enhancing cancer cell death without killing hepatocytes are potentially useful adjuvants of anti-HCC treatments. Flavones, plant-derived natural products, are potent adjuvants due to their cancer selective property. This commentary will discuss current challenges of HCC treatments and the potential use of flavones as adjuvants of HCC treatments.