Objective  To investigate the efficacy of tacrolimus combined with entecavir in the treatment of patients with nephrotic syndrome with hepatitis B and its effect on angiopoietin like protein-4 (Angptl4), 24-hour proteinuria and glutamic pyruvic transaminase (GPT).Methods  From January 2016 to January 2021, 85 patients with nephrotic syndrome complicated with hepatitis B were prospectively analyzed in our hospital. The patients were divided into control group (43 cases) and study group (42 cases) by using the number table method. The control group received tacrolimus treatment, and the research group received tacrolimus combined with entecavir treatment. The efficacy of the two groups of patients was compared.Results  The significant efficiency and effective rate of the study group were 66.67% (28 cases) and 28.57% (12 cases), respectively, while those of the control group were 48.84% (21 cases) and 30.23% (13 cases). The total effective rate of the study group was higher than that of the control group (95.24% vs. 79.07%，P=0.026). Before treatment, there were no statistically significant differences in the levels of GPT, ALP, GGT, serum blood glucose, albumin, 24-hour proteinuria, Angptl4, Th17, Th1, and serum T lymphocyte subsets between the two groups (all P>0.05). After treatment, the levels of GPT, serum blood glucose, 24-hour proteinuria, Angptl4, Th17, Th1 and CD4⁺ in the two groups were lower than those before treatment, while the levels of ALP, GGT, albumin and CD8⁺ were higher than those before treatment, and the level of CD4⁺/CD8⁺ in the control group was lower than that before treatment (all P>0.05). After treatment, ALP, GGT, albumin, serum CD4⁺, CD4⁺/CD8⁺ levels in the study group were higher than those in the control group, and GPT, serum blood glucose, 24-hour proteinuria, serum Angptl4, Th17, Th1, CD8⁺ were lower than those in the control group (all P<0.05). There was no significant difference in adverse reactions between the two groups (χ²=0.298，P=0.585).Conclusions  Tacrolimus combined with entecavir in the treatment of nephrotic syndrome complicated with hepatitis B can effectively improve the T lymphocyte subsets of patients, improve liver and kidney function, reduce the level of Angptl4, and has good safety.