There are two classes of antiviral drugs for chronic hepatitis B: interferons and nucleoside (acid) analogs. The advantage of interferon, especially long-acting interferon, is that it has a limited course of treatment and a higher chance of achieving e antigen conversion, i.e., major triplet to minor triplet, or even surface antigen clearance, so the chance of stopping the drug is greatly increased. Many patients who have learned about this feature of interferon decide to undergo this treatment in the hope that they will be the “lucky ones”. Over the years, the results of clinical studies on the antiviral treatment of chronic hepatitis B have been increasing, and the treatment and efficacy of interferon against hepatitis B virus, represented by pegylated interferon, has made great progress, raising the initial virological response to HBeAg serological conversion, and then to the disappearance of HBsAg and serological conversion, setting a clear goal for the antiviral treatment of chronic hepatitis B. However, after a period of treatment some patients do not achieve the expected results and they become discouraged or even give up interferon therapy outright. Interferon is a biological agent, an immunomodulator, and different individuals respond differently to interferon, but current clinical studies have confirmed that long-acting interferon is the best choice to help patients with chronic hepatitis B achieve the first-line treatment option of converting major triplets to minor triplets. Using long-acting interferon is of course expected if the efficacy is ideal, but if the efficacy is temporarily unsatisfactory, the treatment plan should be actively adjusted to maximize the efficacy of the drug for better results. In this case, what should be done is the following: First, communicate with the doctor to review the past medication to see if there is a shortage of dose and number of doses, and if there are adverse reactions that affect medication compliance because of fever and other adverse reactions, you should promptly ask the doctor to help solve the problem. Secondly, follow up on time as prescribed by the doctor and keep detailed records of various responses after medication administration. Studies have confirmed that the two indicators that best predict the ultimate efficacy of long-acting interferon are the surface antigen, which is now available in many places for quantitative testing, and based on the results of quantitative testing, doctors can make more accurate judgments. For example, in a large-scale study, the results showed that if the surface antigen was reduced to less than 1500 IU/ml at 24 weeks of pegylated interferon treatment, the patient’s 24-week e antigen persistence conversion rate was 54% at the end of 48 weeks of treatment, while this rate was relatively low in other patients. Therefore, clinical experts recommend different treatment strategies for patients with different responses after 24 weeks of long-acting interferon therapy. For patients with good responses, i.e., surface antigen levels below 1500 IU/ml, they only need to continue treatment until 48 weeks, while for other patients, they should consider combination nucleoside (acid) therapy or plan to extend the course of long-acting interferon therapy. Studies have shown that combination or extended therapy can effectively improve the efficacy of long-acting interferon, which is more reasonable than giving up long-acting interferon directly. Finally, take advantage of the discontinuation point. The results of the study found that the e antigen and surface antigen status at the time of discontinuation of long-acting interferon can predict the stability of the efficacy after discontinuation, and some studies suggest that patients whose e antigen has been converted at the time of discontinuation and whose surface antigen is less than 10 IU/ml have very good stability after discontinuation. If there is still a large gap in efficacy after completing a regular course of interferon, extended treatment or combination or continuation of nucleoside (acid) analogue therapy can be considered depending on the specific condition. In conclusion, because of the huge difference in the half-life of free virus clearance, clearance of virus-infected hepatocytes and clearance of hepatic HBV-DNA in patients with chronic hepatitis B treated with interferon, the treatment of patients, especially interferon-based antiviral therapy, has been determined by whether or not lasting immune control is achieved, and patients with a good response to treatment pursue higher immune control goals, or even obtain a “clinical cure. In order to achieve higher immune control goals for patients with a good response, or even to achieve a “clinical cure”, more patients need to extend their treatment to achieve their goals, and individualized treatment can maximize their chances of achieving immune control. The success of the treatment of long-acting interferon does not happen overnight, but requires skill and a good treatment strategy to maximize efficacy.