Drug resistance is an important barrier to the efficacy of anti-hepatitis B virus therapy with nucleoside (acid) analogues. When nucleoside (acid) analogues are used for long-term treatment, drug resistance occurs more commonly. Drug resistance can not only lead to loss of therapeutic benefits (e.g., histological improvement), but also to dramatic deterioration of liver lesions and disease progression (e.g., hepatitis flare-up, liver failure, liver failure, etc.). Several studies have shown that the incidence of cirrhosis and hepatocellular carcinoma is significantly higher in drug-resistant patients than in non-drug-resistant patients. Cross-resistance and multi-drug resistance will increase the difficulty of subsequent treatment and limit the options for re-treatment.