Liver fibrosis and hepatocellular carcinoma (HCC) have been worldwide threats nowadays. Liver fibrosis is reversible in early stages but will develop precancerosis of HCC in cirrhotic stage. In pathological liver, excessive H2O2is generated and accumulated, which impacts the functionality of hepatocytes, Kupffer cells (KCs) and hepatic stellate cells (HSCs), leading to genesis of fibrosis and HCC. H2O2accumulation is associated with overproduction of superoxide anion (O2•−) and abolished antioxidant enzyme systems. Plenty of therapeutics focused on H2O2have shown satisfactory effects against liver fibrosis or HCC in different ways. This review summarized the reasons of liver H2O2accumulation, and the role of H2O2in genesis of liver fibrosis and HCC. Additionally, nanotherapeutics targeting H2O2were summarized for further consideration of antifibrotic or antitumor therapy.