Existing anti-HBV drugs cannot completely remove intracellular covalent closed circular DNA (cccDNA), once the drug is stopped, cccDNA can be used as a template for HBV replication to re-transcribe and replicate, resulting in “relapse”. All kinds of nucleoside (acid) drugs have the situation of relapse after stopping the drug, 24 weeks to 2 years after stopping the drug follow-up, virological relapse rate is generally in the range of 50% to 60%. China’s nucleoside (acid) drug treatment population is huge, with the largest number of LAM treatment patients, the incidence and frequency of nucleoside (acid) drug resistance in treated patients are significantly higher than the first treatment patients, nucleoside (acid) drug treatment response is not ideal and virological breakthroughs of quasi-species complexity increases, there have been a number of resistance sites quasi-species of the case of switching to drug treatment, drug selective pressure in the drug can be rapidly occurring resistance, so that antiviral drugs lead to quasi-species of resistance. Therefore, antiviral drugs lead to quasispecies change and/or resistant strain generation, which affects the efficacy of subsequent treatment and makes re-treatment more difficult, and the patient’s confidence in treatment decreases, and the chances of successful discontinuation of the drug are even smaller. With the prolongation of the treatment time, the adherence of the treated patients also decreases, and surveys have shown that only 80% of them remain adherent to the treatment at the end of 12 months, so the situation of the patients with treated relapses is very complicated. Studies have shown that the risk of resistance is significantly increased in LAM-treated patients switching to ETV monotherapy, regardless of whether prior LAM resistance has occurred [Hepatology. 2011; 54(S1):1042A]. patients with LAM-treated non-resistant and LAM-resistant patients switching to ETV (doses of 0.5 mg/d and 1.0 mg/d, respectively) monotherapy. The incidence of ETV resistance at week 192 was as high as 18% and 47%, respectively, with no statistical difference between the two groups. For patients who relapsed after LAM discontinuation, retreatment with the combination regimen of LAM+ADV achieved satisfactory efficacy, and the virological response rate (HBV DNA <1000 copies/ml) at 6, 9 and 12 months of treatment was significantly better than that of the LAM monotherapy group, and the virological response rate, HBeAg conversion rate and HBeAg seroconversion rate at 12 months were as high as 80%, 36% and 28%, respectively. The rates of virologic response, HBeAg conversion, and HBeAg seroconversion at 12 months were as high as 80%, 36%, and 28%, respectively, and none of the patients experienced virologic breakthrough, and no LAM- or ADV-resistance mutations were detected. Another study showed that the efficacy of the ETV+ADV combination regimen was significantly better than that of ETV monotherapy in patients who were still poorly treated with ADV after LAM resistance. Therefore, relapse after drug discontinuation is a common problem in the antiviral treatment of chronic hepatitis B patients, and should be actively retreated, and the earlier the time of intervention, the better; unlike primary patients, relapsed patients should avoid single-drug sequential therapy. The application of LAM+ADV combination therapy in nucleoside analogs-treated patients showed high virologic and serologic response rates, reduced occurrence of drug resistance, good patient tolerance, less economic burden, and sufficient evidence of evidence-based medicine.