In Japan, hepatitis C virus (HCV) is the single most frequent cause of hepatocellular carcinoma (HCC), resulting in yearly deaths of over 30,000. Although the mechanism of how HCV induces HCC is not clear, persistent HCV infection and necro-inflammatory changes in chronic hepatitis C accelerate the development of liver cirrhosis and can eventuate in HCC. Hence, means of eradicating HCV as well as suppressing inflammation in the liver, even if patients stay infected with HCV, would decrease the incidence of HCC with chronic hepatitis C. For more than 40 years, a preparation of glycyrrhizin [Stronger Neo-Minophagen C (SNMC)] has been used for the treatment of 'allergic' hepatitis in Japan. In 1977, intravenous injection with SNMC was started in patients with chronic hepatitis or liver cirrhosis, most of whom have turned out to be infected with hepatitis viruses. In a multicenter double-blind study, alanine aminotransferase (ALT) levels decreased in the patients who received 40 ml/day of SNMC for 4 weeks at a rate significantly higher (p < 0.001) than controls receiving placebo. Furthermore, SNMC 100 ml/day for 8 weeks improved liver histology in 40 patients with chronic hepatitis, in correlation with improved ALT levels in serum. Liver cirrhosis occurred less frequently in 178 patients on long-term SNMC than in 100 controls (28 vs. 40% at year 13, p < 0.002). Finally, HCC developed less frequently in the 84 patients on long-term SNMC than in the 109 controls (13 vs. 25% at year 15, p < 0.002). Combined, these results indicate that a long-term treatment with SNMC prevents the development of HCC in the patients with chronic hepatitis. SNMC is particularly helpful in the patients with chronic hepatitis C who fail to respond to interferon and in those who cannot be treated with it for various reasons.