What should be done after drug resistance occurs? Once resistance to oral antiviral drugs is detected, liver function, AFP, quantification of hepatitis B five indexes, quantification of hepatitis B virus, and abdominal ultrasound or CT are needed to accurately assess the condition. If the virus is significantly elevated and there are abnormalities in liver function such as elevated aminotransferases and bilirubin, it is best to be hospitalized for observation, pay attention to rest, and treat with hepatoprotecting and lowering the enzymes; and further carry out multi-resistance analysis of the hepatitis B virus to determine the viral drug resistance variants. Further multi-drug resistance analysis of hepatitis B virus to identify drug-resistant variant of virus, on the one hand, it can further clarify whether it is the recurrence of disease caused by drug resistance of existing drugs, on the other hand, it can also see whether other antiviral drugs not taken are suitable for application, which can help to rationally choose the next step of drugs.