Chronic hepatitis B can affect patients’ work and life, and may even develop into liver cirrhosis and liver cancer, threatening life and health. Obviously, it is the urgent need of every patient to get rid of the disease. So is it possible to “cure” chronic hepatitis B and can patients be completely free from the disease? For chronic hepatitis B, the clinical proxy for “cure” is HBsAg clearance, and those who achieve durable HBsAg clearance are in long-term remission and have very, very little risk of cirrhosis or liver cancer. In contrast, HBsAg clearance in HBeAg-positive patients with chronic hepatitis B (“major triple-positive” patients) mostly occurs after HBeAg seroconversion, which means that HBeAg seroconversion is the basis for HBsAg clearance. The EASL guidelines, the definitive guideline for chronic hepatitis B, also emphasize that the ideal endpoint of treatment for chronic hepatitis B should be durable HBsAg clearance with or without serologic conversion after drug discontinuation, and that the satisfactory endpoint of treatment is durable HBeAg serologic conversion. The key to obtaining HBeAg serologic conversion and HBsAg clearance is immune control, and to achieve this goal, both viral suppression and improving the body’s immunity should be emphasized in treatment. Compared with nucleoside analogues that have only antiviral effects, pegylated interferon, which has a dual mechanism of action, can not only suppress the virus but also control hepatitis B virus infection through immune-mediated control, allowing patients to obtain HBsAg clearance. The results of clinical studies show that pegylated interferon therapy can achieve high HBeAg serological conversion and HBsAg clearance: high and durable HBeAg serological conversion rate Long-lasting HBeAg serological conversion is the basis of HBsAg clearance. Studies have shown that HBeAg serological conversion rates continue to increase after the end of pegylated interferon alpha-2a treatment, with up to roughly 61% of patients achieving HBeAg serological conversion six months after drug discontinuation. Moreover, HBeAg serologic conversion with pegylated interferon alpha-2a has very good durability, with 86% of those patients with HBeAg serologic conversion six months after discontinuation continuing to maintain HBeAg serologic conversion one year after discontinuation. HBsAg clearance is higher HBsAg clearance also continues to increase after the end of pegylated interferon therapy, and among HBeAg-positive patients, 11% will show HBsAg clearance to the desired endpoint of chronic hepatitis B treatment – clinical cure – at 3 years after discontinuation. In particular, among patients with HBeAg clearance at 24 weeks after drug discontinuation, up to 30% achieve HBsAg clearance at long-term follow-up. In conclusion, clinical cure is the best treatment effect for chronic hepatitis B, which can help patients get rid of the disease completely. PEGylated interferon, which has both antiviral and immunomodulatory mechanisms of action, is the preferred treatment option to help patients towards cure, and the correct and standardized application of this drug can enable patients enough to obtain a higher chance of clinical cure.