Nucleoside anti-HBV drugs, currently there are lamivudine, adefovir, tipifovir and entecavir used in the clinic, these drugs, in addition to strong anti-hepatitis B virus, also has the role of normalizing liver function and reducing liver fibrosis. They are easy to use, have no obvious adverse effects, and can be applied by those with indications under the guidance of a specialist physician. However, some hepatitis B patients can develop drug resistance during the long-term application of these drugs. The reason is that the hepatitis B virus genes mutate to become drug-resistant strains and become insensitive to the drugs, which seriously affects the efficacy. Some studies have reported that the earliest drug resistance occurs between the 22nd and 28th week after taking the medication. Within 1 to 2 weeks after the emergence of drug-resistant strains, the level of hepatitis B virus nucleic acid (HBV-DNA) increases significantly, up to 3 orders of magnitude or more, followed by an increase in transaminases and bilirubin, and the appearance of liver function damage. Drug-resistant strains are mainly mutations in the YMDD of the HBV-DNA gene, manifesting as both YIDD and YVDD forms . It is recommended that all patients taking these drugs be dynamically tested for this item, at least every 3 months, to guide treatment. Taking drugs blindly without monitoring is not only a waste of money, but also a lack of good results. If drug resistance occurs, there is no need to worry too much. If resistance occurs with lamivudine, you can switch to or add adefovir, which will curb the resistance and maintain the good efficacy. Therefore, although these new potent antiviral drugs are available for the treatment of hepatitis B, it is important to beware of HBV gene mutations that may affect the efficacy.