Currently, there are two types of antiviral drugs for chronic hepatitis B: long-acting interferons and nucleoside analogs. In general, nucleoside analogs are oral agents that are easy to take and can lower HBV DNA and normalize transaminases relatively quickly, but they need to be taken for a long time or even for life and have a high relapse rate once they are discontinued. Long-acting interferon drugs require injection therapy and may cause some adverse reactions during use, but these drugs also have their distinctive features: they can achieve a high percentage of HBeAg seroconversion and HBsAg clearance within a limited course of treatment, and they can maintain this efficacy for a long time after stopping the drug. Achieving HBeAg serologic conversion and even HBsAg clearance means that patients are clinically cured and can safely discontinue the drug, which is clearly expected. Still, many patients are hesitant when first faced with treatment options and consider whether they are suitable for long-acting interferon therapy. What are the chances of getting a response to long-acting interferon? How do you determine if you are a candidate for interferon therapy? First, in theory, all patients with chronic hepatitis B should prefer long-acting interferon therapy. This is because compared to nucleoside therapy, long-acting interferon therapy has the potential to achieve clinical cure and has a better chance of being safely discontinued with a limited course of therapy. In contrast, if nucleoside therapy is chosen initially, the chances of a relative clinical cure are small, and long-term or even lifelong treatment is usually required. Secondly, the preference for long-acting interferon therapy should be given to patients with superiority. The so-called advantageous patients of interferon therapy are those who can achieve higher e antigen seroconversion (i.e., “major triplet” to “minor triplet”) and clinical cure with long-acting interferon therapy. They are characterized by first-time antiviral treatment for lentivirus B, high enzyme and low toxicity (high transaminase levels and low HBV DNA levels). Clinical studies have confirmed that in HBeAg-positive patients with HBeAg-positive major triple-positive chronic hepatitis B treated for the first time with transaminases above 5 times normal, pegylated interferon alpha-2a treatment for 48 weeks had a HBeAg serological conversion rate of more than 60% at 24 weeks after discontinuation. And such patients can achieve 30% HBsAg clearance at 3 years after drug discontinuation. In addition, in addition to understanding the advantages of long-acting interferon and the characteristics of advantageous patients, it is important to understand that there are some patients who are not suitable for interferon therapy, and these are mainly those with contraindications to treatment, such as allergy to interferon, psychiatric disorders, depression, autoimmune diseases, and those who have developed decompensated cirrhosis. In conclusion, long-acting interferon is the preferred treatment option to achieve clinical cure. Patients with chronic hepatitis B who have no contraindications to interferon treatment can give priority to long-acting interferon therapy, especially those with high enzyme and low toxicity, and should seize the opportunity to achieve safe discontinuation of the drug at the time of initial treatment.