At present, there are two major classes of anti-hepatitis B virus drugs, interferon and nucleoside analogues, the marker of HBV replication is cccDNA in the nucleus of hepatocytes, nucleoside analogues can only inhibit the replication of HBV, but have little effect on the clearance of cccDNA. Therefore, the application of nucleoside analogs takes many years to clear cccDNA, but many patients develop viral mutations before cccDNA is cleared. Interferon can clear intracellular cccDNA by cytolytic and non-cytolytic immune clearance modes with limited duration of therapy and low relapse rate after obtaining seroconversion, but the efficacy is still relatively low, and studies have shown that Peg interferon can be HbeAg/anti-HBe seroconversion for HBeAg-positive chronic hepatitis B up to 30-40%, and has more side effects. Therefore, the combination of antiviral therapeutics is receiving increasing attention from clinical experts, but further evidence from evidence-based medicine is still to be found. Firstly, combinations between nucleoside analogues are relatively common and have been shown to reduce the rate of HBV resistance, but there is only some evidence of combinations of drugs with low genetic resistance disorders (lamivudine, adefovir). Combination therapies may achieve greater suppression of HBV replication, but this has not been achieved with higher seroconversion rates (hepatitis B e antigen or hepatitis B surface antigen). Application of drugs with high genetic variation barriers (tenofovir, entecavir) needs to be further explored. Combination therapy between nucleoside analogs is indicated for specific patient groups: those with cirrhotic decompensation, those with human immunodeficiency virus and hepatitis B virus who are on antiretroviral therapy for coinfection, those who have undergone liver transplantation, and those with drug-resistant HBV infection. For interferon combined with nucleoside analogue therapies should be given more attention, Peg interferon combined with lamivudine after 48 weeks leads to more complete clearance of HBV DNA, obtaining higher clearance of infected HBV hepatocytes, higher HBVDNA negative rate and HbeAg/anti-HBe conversion rate than with drugs alone, but this HBV index of 24 weeks after treatment cessation The difference between the HBVDNA negative conversion rate and HbeAg/anti-HBe conversion rate between patients on the single agent and the combination was not significant, but some experts believe that the design of this subject is flawed and the treatment course is too short, especially since lamivudine should not be discontinued after 1 year of application. Another study of Peg interferon combined with adefovir for HBeAg-positive chronic hepatitis B for 144 weeks (Peg interferonα2a for 48 weeks and adefovir for 144 weeks) showed a 2.4log decrease in hepatocyte cccDNA and 53.3% and 16.6% seroconversion rates for Hbeg and HBsAg, respectively, in the combined treatment group and 16.6%, respectively. No evidence-based medical reports have been seen on combination regimens of entecavir in combination with other antivirals, as combination therapy with nucleoside analogs with high resistance genetic barriers and high efficacy has the potential to achieve higher antiviral response rates. In conclusion, until new breakthroughs in anti-HBV drugs are achieved, the current trend of combination therapy with antiviral drugs is a trend, but how to combine in order to obtain higher response rates and to have more favorable goals for obtaining treatment for chronic hepatitis B is a topic that deserves further exploration.