Abstract：Objective：To observe the clinical effect of point application combined with Piperacillin and Tazobactam for sepsis. Methods：A total of 566 cases of children with sepsis were retrospectively selected and divided into the control group and the observation group according to different treatment methods， with 283 cases in each group. Both groups were given symptomatic treatment； the control group was given intravenous infusion with Piperacillin and Tazobactam， and the observation group was additionally treated with point application based on the treatment of the control group. The clinical effects in the two groups were evaluated； the severity of disease， inflammation levels， and immune function were compared between the two groups. Results： The total effective rate was 95.76% in the observation group， higher than that of 80.57% in the control group， the difference being significant (P＜0.05). After treatment，the scores of Acute Physiology and Chronic Health Evaluation (APACHEⅡ) and Marshall scores of multiple organ dysfunction in the two groups were decreased when compared with those before treatment (P＜0.05)；APACHEⅡ score and Marshall score in the observation group were lower than those in the control group (P＜0.05). After treatment，the levels of interleukin-6 (IL-6)，tumor necrosis factor-α (TNF- α)， and C- reactive protein (CRP) in the two groups were decreased when compared with those before treatment (P＜0.05)，and the levels of IL-6，TNF-α，and CRP in the observation group were lower than those in the control group (P＜0.05). After treatment，CD3+，CD4+，and CD4+/CD8+ in the two groups were increased when compared with those before treatment (P＜0.05)，and the CD3+，CD4+，and CD4+/ CD8 + in the observation group were higher than those in the control group (P＜0.05). Conclusion： Point application combined with Piperacillin and Tazobactam for pediatric sepsis can reduce the severity of disease and inflammatory responses，improve immune function，and enhance the clinical effect.