At present, there are four nucleoside (acid) analogs used for the treatment of chronic hepatitis B in China: lamivudine (LAM), adefovir (ADV), telbivudine (LdT) and entecavir (ETV), and the fifth nucleoside (acid) analog, tenofovir (TDF), has been approved for marketing in China. Nucleoside analogs are inhibitors of HBV, and they do not completely remove HBV from the body, so they need to be taken for a long time when chronic hepatitis B patients are treated with nucleoside analogs. Long-term management and attention to many issues, such as the efficacy of antiviral therapy, the risk of drug resistance, patient compliance and safety, are required during long-term administration of nucleoside analogs. In general, nucleoside analogs have fewer adverse effects, are well tolerated, and have a lower rate of treatment interruption. What are the adverse effects of taking nucleoside analogs? Common adverse reactions include fatigue, nausea, headache, rash, abdominal pain or diarrhea, etc. These symptoms are mild, occur less frequently, and do not require treatment such as stopping the drug or reducing the dosage. However, each person’s body condition is different, some patients taking nucleoside (acid) drugs can occur creatinine clearance abnormalities, creatine kinase, amylase and lipase levels increased. In the long-term treatment of patients with chronic hepatitis B, special attention should be paid to the health of vital organs such as kidney, heart and bones: chronic HBV infection is closely related to decreased bone density, and osteoporosis is a common symptom in patients with cirrhosis of hepatitis B. In patients with type 2 diabetes mellitus, chronic HB/infection can increase the risk of end-stage renal disease in the patients: medications with nephrotoxicity may further increase the renal risk of kidney injury. Therefore, whether long-term treatment can be achieved in patients with chronic hepatitis B depends on their overall health status, and some patients may discontinue treatment due to intolerance or even develop more serious health impairments. A potential side effect of nucleoside (acid) analogs is the possibility of abnormal mitochondrial function. Clinical manifestations associated with mitochondrial toxicity due to nucleoside analogs include, for example, neuropathy, myopathy, hepatocellular steatosis, nephrotoxicity, hyperlactatemia or lactic acidosis, acute pancreatitis, hematologic disorders, and cardiomyopathy. All nucleoside (acid) analogs have a black box warning about mitochondrial toxicity in the drug insert.