With the wide application of nucleoside (acid) drugs, the prognosis of chronic hepatitis B has been greatly improved. However, how to standardize the application of this class of drugs is indeed another difficult problem faced by clinicians. At present, there are four drugs in this class in China: lamivudine, tibivudine, adefovir and entecavir. These four drugs have different viral suppression activity, drug resistance mutation rate and their prices. Clinicians should choose a drug that best suits the patient’s condition according to the patient’s actual condition, such as peak ALT AST, high or low viral load, e-antigen positive or e-antigen negative, and the patient’s age, etc. Never abuse the drug to avoid increasing drug resistance. Remember to abuse it so as not to increase the rate of drug-resistant mutation and make the treatment more difficult in the future. Particular attention should be paid to the application of nucleotide analogs in patients of childbearing age. If the patient has no contraindications, it is recommended that interferon be the first choice for patients of childbearing age who are not planning a pregnancy in the near future.