Patients who know more about hepatitis B know that hepatitis B is caused by the hepatitis B virus (HBV), and they will be worried when they see high HBV DNA levels on their labs. HBV DNA is the abbreviation for hepatitis B virus deoxyribonucleic acid. The result on the lab report reflects the level of HBV DNA in the serum, and usually the higher the value, the more active the HBV replication in the liver. However, this does not necessarily mean that the disease is more severe. Chronic hepatitis B is an immune-mediated disease. For example, during the immune tolerance period, the body’s immune system “coexists peacefully” with HBV, and even though HBV DNA levels are high at this time, they do not cause inflammatory damage to liver cells, and doctors usually tell patients that they do not need treatment yet. The immune tolerance period is a period in the process of slow hepatitis B infection. As the immune system matures with age, it may enter the immune clearance period, where “peaceful coexistence” becomes “incompatible” and the body’s immune system begins to take the initiative to attack and try to remove HBV from the liver. The liver becomes the main battlefield, causing hepatitis, which is manifested by elevated transaminases. At this stage, it is necessary to start antiviral therapy to help the body clear the virus as much as possible. Checking HBV DNA levels after starting antiviral therapy can help doctors determine the effectiveness of drug therapy. Nucleoside (acid) analogue therapy focuses on direct suppression of viral replication, and the goal of treatment is to reduce HBV DNA to undetectable levels. Nucleoside (acid) analogs require long-term treatment, so it is necessary to monitor HBV DNA levels regularly after starting this treatment to see if the treatment continues to be effective, and if HBV DNA decreases and then increases during treatment, drug resistance may have occurred and needs to be addressed promptly. Unlike nucleoside (acid) analogs, the mechanism of interferon therapy is to directly “boost” the body’s immune system to control viral replication through immunity. To monitor the efficacy of interferon therapy, in addition to observing HBV DNA levels, we must also look at changes in E and surface antigen levels, the latter two indicators better reflecting the immune status of the body compared to HBV DNA. Successful interferon treatment results in a negative or persistently low level of HBV DNA, serological conversion of E antigen, and even clearance of surface antigen at the end of treatment. In conclusion, we need to have a comprehensive understanding of HBV DNA, understand the significance of HBV DNA changes at different stages of the disease and under different treatment regimens, actively communicate with our doctors, and cooperate well with treatment and follow-up.