Objective: To study the efficacy of entecavir in the treatment of patients with chronic hepatitis B and its effect on the expression level of Th1/Th2 cytokines in the peripheral blood. Methods: Chronic hepatitis B patients who were admitted to the outpatient department of our hospital from March 2018 to December 2019 and the healthy controls from the same period were selected and divided into an observation group (110 cases) and a control group (57 cases). The control group was treated with adefovir dipivoxil and the observation group was treated with entecavir. The changes of Th1/Th2 cytokine expression levels in the two groups and the relationship between the expression level of each cytokine, each cytokine and HBV DNA load were observed. Results: In the observation group, 3.64% of patients were diarrheal, which was significantly lower than the control group; 0 patients experienced nausea and vomiting, which was significantly lower than the control group; 3.64% of patients experienced giddiness, which was lower than the control group; the total incidence was 8.18%, which was significantly lower than the control group (P<0.05 ). In the observation group, the ineffective rate was 3.64%, which was significantly lower than 24.56% in the control group; the total effective rate was 96.36%, which was significantly higher than 75.44% in the control group (P<0.05). The expression level of Th1 cytokine IFN-gamma in the peripheral blood of patients with hepatitis B before antiviral treatment was significantly higher than that of the control group (P<0.05). Compared with the control group, there was no significant difference in the TNF-alpha expression level of the observation group (P<0.05). The expression levels of Th1 cytokines IFN-gamma and TNF-alpha in the peripheral blood of patients with hepatitis B decreased significantly after ETV antiviral treatment (P<0.05). The expression levels of Th2 cytokines IL-4, IL-6 and IL-10 in patients with hepatitis B were significantly lower than those in the control group (P<0.05). The expression levels of Th2 cytokines IL-4 and IL-6 increased after treatment. Conclusion: Entecavir antiviral therapy can regulate the expression level of Th1/Th2 cytokines in peripheral blood, inhibit the replication of HBV DNA and reduce viral load, however, there is no correlation between each cytokine, HBV DNA load and the expression level of each cell.