ETHNOPHARMACOLOGICAL RELEVANCE: Shenfu injection (SFI) is a well-known Chinese herbal medicine widely used in the treatment of septic shock in China. AIM OF THE STUDY: To explore the clinical safety and effectiveness of combined application of Shenfu injection in the treatment of septic shock on the basis of routine western medical treatment. MATERIALS AND METHODS: Randomized controlled trials published before February 28, 2022 in patients with septic shock were searched in the Chinese Biomedical Literature Service System (SinoMed), Embase, PubMed, Cochrane Library, WOS, Scopus. Stata 15.0 and R 4.2.2 were used to meta-analyze sequential organ failure assessment (SOFA) score, case fatality rate, mean arterial pressure (MAP), arterial lactate (Lac). Adverse effects were analyzed by description. RESULTS: A total of 904 articles were searched and 56 RCTs were included, with a total of 4279 participants. Among them, there were 2148 cases in the SFI group and 2131 cases in the control group. The meta-analysis showed that, comparing with routine western medical therapy, the combined use of SFI could effectively reduce 24 h SOFA (MD = -0.79, 95%CI: (-1.12) - (-0.46)), 72 h SOFA (MD = -1.53, 95%CI: (-1.89) - (-1.17)) and 7 d SOFA (MD = -1.55; 95%CI: (-2.86) - (-0.24)). Besides, combined use of SFI could reduce 14 d case fatality rate (RR = 0.16, 95% CI: 0.07-0.37) and 28 d case fatality rate (RR = 0.82, 95% CI: 0.71-0.95). While SFI group showed almost the same effect in 7 d case fatality rate as control (RR: 0.76; 95% CI: 0.42-1.37; P = 0.37). SFI could increase 6 h MAP (MD = 6.40, 95% CI: 3.43-9.37) and 24 h MAP (MD = 4.79, 95% CI: 1.62-7.95). Additionally, SFI could decrease 6 h Lac (MD = -0.90, 95% CI: (-1.34) - (-0.45)), 24 h Lac (MD = -0.80, 95% CI: (-1.20) - (-0.40)), 48 h Lac (MD = -0.67, 95% CI: (-1.05) - (-0.29)). CONCLUSIONS: Shenfu injection combined with RWT showed better therapeutic effect than RWT. SFI plus RWT can improve clinical prognosis of patients with septic shock.