Objective: To observe the effect of Elephantopus scaber Linn on community-acquired pneumonia and its relationship with the expression of TLR4/NF-κB pathway and the downstream inflammatory cytokines IL-6, IL-8, TNF-α. and to explore its molecular mechanism for the treatment of community-acquired pneumonia, so as to provide new ideas and theoretical basis for the treatment of community-acquired pneumonia. Methods: 140 patients with community-acquired pneumonia were randomly divided into observation group and control group, with 70 cases in each group. Observation group: Elephantopus scaber Linn + NS atomized inhalation + intravenous injection of ceftazidine; Control group: intravenous injection of ceftazidine; Meanwhile, 70 healthy subjects were selected as the healthy control group. The expressions of TLR4, NF-kB, IL-6, IL-8 and TNF-αin serum of observation group, control group before and after treatment and healthy control group were detected by enzyme linked immunosorbent assay (ELISA), and the efficacy of Elephantopus scaber Linn in the treatment of community acquired pneumonia was observed. Results: Compared with the control group, the observation group was significantly better than the control group in recovery rate, total effective rate, number of days for the disappearance of symptoms such as fever, cough, expectoration, with statistical significance (P<0.05); Compared with the healthy control group, the serum TLR4, NF-κB, IL-6, IL-8, TNF-αwere significantly different(P<0.05) between the observation group and the control group; Serum TLR4, NF-κB, IL-6, IL-8, TNF-α were significantly different(P<0.05) in the observation group before and after treatment with Elephantopus scaber Linn; Compared with the control group after treatment, there were significantly different(P<0.05) in serum TLR4, NF-κB, IL-6, IL-8 and TNF-α in the observation group after treatment. Conclusion: Serum TLR4, NF-κB, IL-6, IL-8, TNF-α were highly expressed in patients with community-acquired pneumonia, Elephantopus scaber Linn can decreased the expression of TLR4 and NF-κB in blood, and its downstream inflammatory factors also decreased significantly. There were significantly different(P<0.05) in blood TLR4 and NF-κB between the observation group and the control group after treatment. It is suggested that Elephantopus scaber Linn may inhibit TLR4/NF-kB signal pathway to exert anti-inflammatory effect. Elephantopus scaber Linn has a definite effect and can significantly improve the clinical symptoms, and effectively shorten the treatment cycle.