It has been more than 10 years since nucleoside (acid) drugs have been used in clinical practice. There is no clearly defined period of time to recognize the discontinuation of nucleoside analogs, regardless of domestic and foreign guidelines. The drug has been used for several years, liver function has long been normal, HBV DNA also turned negative, in the end can stop the drug? In the current guideline of China, the recommendation of stopping nucleoside analogs is: Hepatitis B “triple positive” patients, after achieving HBeAg conversion, continue to consolidate the treatment for more than 1 year before considering stopping the drug, but prolonging the course of treatment can reduce the recurrence of the disease. For patients with “triple positive”, it usually takes 3-5 years of treatment before HBeAg conversion can occur. Patients with small triple positive have more insidious disease despite better antiviral efficacy. Although nucleoside therapy can reduce serum HBsAg levels from pre-treatment levels, it is difficult to achieve conversion. These patients often need long-term treatment, and even if the criteria for stopping the drug are met, the serum HBV DNA level of some patients will increase after stopping the drug, which will eventually lead to the recurrence of hepatitis. Therefore, the ability to safely stop the drug is always a problem for nucleoside analog therapy. Nucleoside (acid) drugs lack the regulation of the body’s immune function, nucleoside (acid) drug therapy is difficult to obtain lasting immune control, is a major cause of nucleoside (acid) drugs easy to relapse after discontinuation. In contrast, interferons, especially long-acting interferons, have a dual mechanism of action of immune modulation and direct antiviral action, which helps to achieve immune control and long-term remission of slow hepatitis B. In the phase III clinical study of pegylated interferon alpha-2a (long-acting interferon), 86% of patients who experienced HBeAg serologic conversion at 24 weeks after discontinuation of the drug were able to maintain their response after 1 year. Therefore, it has been asked whether interferon can be applied to help nucleoside-treated patients achieve safe discontinuation. Current studies have shown that PEG interferon can shorten the treatment course of nucleoside (acid) analogs, and that switching to or adding PEG interferon α-2a to nucleoside (acid) analogs-treated patients can achieve durable immune control through a limited course of treatment, HBeAg seroconversion or even HBsAg clearance, and ultimately achieve the goal of safe discontinuation of long-term remission and improved clinical outcomes. The results of a national study have confirmed that HBsAg clearance can reach 25% after switching to pegylated interferon alpha-2a for those who have been treated with nucleoside (acid) analogs and have achieved undetectable HBV DNA, HBeAg clearance, and low levels of HBsAg. Lasting response is the higher pursuit of chronic hepatitis B treatment. Seeking advice from a medical professional to develop an individualized strategy for interferon therapy based on response to nucleoside (acid) analogs is currently the most likely treatment option to meet the patient’s expectations for discontinuation.