PEGylated interferon alpha-2a has achieved good efficacy in the treatment of chronic hepatitis B by virtue of its direct antiviral and immunomodulatory effects, and has now become the first-line drug for the treatment of chronic hepatitis B. PEGylated interferon alpha-2a is a biological agent, and there are certain adverse effects in its use. However, through long-term clinical practice and a large number of research records, the adverse effects of pegylated interferon alpha-2a have been very clear and can be effectively controlled and managed, and for most patients will not affect the normal treatment. The most common adverse reactions to pegylated interferon alpha-2a are flu-like symptoms, mainly manifested as fever and chills, headache, muscle aches and weakness. They usually appear at the beginning of the first or second treatment with pegylated interferon alpha-2a, and can gradually decrease or even disappear with the extension of the treatment time. When flu-like symptoms occur, when the body temperature is lower than 38.5 ℃, you can drink more water and use sprinkler baths and other methods of physical cooling. When the body temperature is higher than 39℃, bed rest and antipyretic and analgesic drugs are needed to relieve the symptoms. A decrease in peripheral blood leukocytes and platelets may occur in the early stage of treatment with pegylated interferon alpha-2a, and most of them can recover on their own without affecting the treatment. Usually, the dose of the drug should be adjusted downward only if the total white blood cell count is ≤1.5×109/L or neutrophils ≤0.75×109/L or platelet count ≤50×109/L. In order to detect adverse reactions in a timely manner, routine blood tests should be performed weekly before and during treatment to understand the blood picture, and the dose can be reduced if necessary according to the doctor’s judgment. Thyroid function abnormalities are another common adverse effect of pegylated interferon alpha-2a treatment, which requires regular monitoring of thyroid function or thyroid autoantibodies and other related indicators. For patients who have their own thyroid disease, interferon therapy can be continued at the same time as the treatment of thyroid disease. Some patients may experience depression, headache, insomnia and irritability, emotional disorders, mood changes and other mental abnormalities during pegylated interferon alpha-2a treatment. Patients should establish the information to overcome the disease and seek help from the doctor in time, timely symptomatic treatment can improve the symptoms very well. Only a very small number of patients who develop severe psychiatric abnormalities need to interrupt treatment. Of particular concern is the elevation of ALT during pegylated interferon alfa-2a treatment. transient elevations of ALT are very common in pegylated interferon alfa-2a treatment of chronic hepatitis B and can exceed the upper limit of normal by up to ten times. Studies have shown that the higher rate of virologic response in those with elevated ALT early in treatment is a result of the immune mobilization of the body by pegylated interferon alfa-2a. Instead of discontinuing the drug at this point, treatment should be continued because it is a pointer to effective treatment. The doctor will continue treatment with close monitoring of ALT and bilirubin. In conclusion, like various other drugs, the use of pegylated interferon alpha-2a can have adverse effects, but the vast majority of them do not interfere with normal treatment. Before treating chronic hepatitis B with pegylated interferon alpha-2a, patients should have good communication with their doctors to understand the course of treatment, its efficacy, as well as the possible adverse reactions and preventive treatment methods to be aware of them. In the process of treatment to establish confidence, timely communication with the doctor of the occurrence of adverse reactions, adhere to treatment, do not easily stop the drug will eventually be able to achieve good results.