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Objective: To explore the effect of switching to sequential treatment of tenofovir disoproxil in patients with chronic hepatitis B HBeAg (+) who have a poor response to treatment, and to provide a theoretical basis for better clinical treatment of chronic hepatitis B HBeAg (+) patients. Methods: Totally 90 patients with chronic hepatitis B HBeAg (+) treated in our hospital from December 2016 to December 2018 were selected as the research subjects and randomly divided into the extension group treated tenofovir disoproxil fumarate tablets and the diversion group treated with tenofovir disoproxil, 45 cases in each group. Compare the statistical differences of the content of HBeAg and HBV-DNA, liver function indicators (TBIL, TC, INR ratio), serological and biochemical responses, adverse reactions (gastrointestinal symptoms and nausea / weakness, rash) in the two groups of patients before and after treatment. Results: Comparing the efficacy of the 12-month extension group with the diversion group. It was found that the HBeAg (0.69 ± 0.10PEI / mL) and HBV-DNA (3.26 ± 0.94IU / mL) in the diversion group were lower than those in the extension group (0.90 ± 0.17 PEI / mL) and HBV-DNA (4.37 ± 1.26IU / mL), and the differences were statistically significant (P <0.05). Comparing the efficacy of the 12-month extended group with the diversion group, it was found that the TBIL content in the diversion group (1035.72 ± 92.44umol / L) was higher than that in the extension group (234.72 ± 27.56umol / L) and the the TBILINR ratio was lower (2.70 ± 0.39), and the differences were statistically significant (P <0.05). Comparing the 12-month difference between the extension and diversion groups, it was found that the HBeg reversion rate in the diversion group (36 cases, 80.00％) was higher than that in the extended group (27 cases, 60.00％), and the HBeg LT recovery rate It was also higher than the extended use group (22 cases, 48.89％), and the differences were statistically significant (P<0.05). The incidence of adverse reactions in the extension group (17 cases, 37.78％) was higher than that in the diverted group (8 cases, 17.78％), and the difference was statistically significant (P <0.05). Conclusion: For patients with chronic hepatitis B HBeAg (+) with poor response to treatment, switching to tenofovir disoproxil sequential treatment can not only improve the treatment effect, but also effectively reduce the occurrence of adverse reactions.