In the antiviral treatment of chronic hepatitis B, the nucleoside class includes five drugs: entecavir, tenofovir, telbivudine, adefovir and lamivudine. The antiviral strength of the drugs and the resistance mutation rate are important indicators for the selection of nucleoside analogs. Entecavir and tenofovir are drugs with strong antiviral activity and low incidence of resistance mutation, which are recommended as first-line drugs in domestic and international guidelines. The choice of entecavir or tenofovir for primary care patients can rapidly inhibit viral replication. For example, for patients with high serum viral levels or severe inflammatory lesions, entecavir and tenofovir are preferable; for patients with critical conditions and liver transplantation, entecavir and tenofovir should be preferred. Characteristics of the five nucleoside analogues: Indicators: Lamivudine; Adefovir; Entecavir; Tibivudine; Tenofovir. Dose (per tablet): 100mg; 10mg; 0.5mg; 600mg; 300mg. HBV DNA conversion rate (1 year of treatment): 50-60%; 40-50%; 80%; 70%; 90%. e antigen serological conversion rate (1 year of treatment): 16-18%; 12-18%; 21%; 22%; 21%. Resistance mutation rate: 66% at 4 years; 20% at 5 years; 1.7% at 3 years; 24% at 2 years; 0 at 3 years; Adverse effects: few. Potential nephrotoxicity: few. Potential neuromuscular toxicity: potentially nephrotoxic but less than adefovir. Even for entecavir and tenofovir, which have the strongest antiviral activity, the rate of achieving e antigen clearance versus serologic conversion is still low, and discontinuation of the drug predisposes to relapse. This is the main limitation of nucleoside therapy. Therefore, patients who choose nucleoside analog therapy should be prepared for long-term treatment, even lifelong treatment. Recent clinical studies have confirmed that patients who have responded to nucleoside therapy, especially those with HBV DNA conversion, e antigen clearance and low levels of surface antigen, can be considered for long-acting interferon therapy to shorten the course of treatment and strive for discontinuation. In conclusion, there are many types of nucleoside drugs and each drug has its own characteristics. Patients should choose the drugs according to their own situation under the guidance of their doctors. For some nucleoside treated patients with discontinuation problems, long-acting interferon therapy can be considered to achieve the purpose of helping to discontinue the medication.