Abstract： Objective： To study the mechanism of Huatan Tongfu Prescription on anti-inflammatory reactions and prognosis in patients with sepsis-associated lung injury through TGF - β1 / Smad3 signaling pathway. Methods： A total of 80 patients with sepsis-associated lung injury were included into this prospective study，from March 2019 to December 2022. The study subjects were divided into two groups according to the random number table method， with 40 cases in each group. The control group received basic treatment， and the study group was treated with Huatan Tongfu Prescription based on basic treatment. Both groups were treated for 5 days. The 28-day mortality rates based on 1-month follow-up results， the curative effects， Intensive Care Unit (ICU) hospitalization， and mechanical ventilation time were compared between the two groups. The sepsis symptom scores， oxygenation index (PaO2 / FiO2)， alveolar -arterial oxygen gradient [Pa (A-a) O2]， and levels of tumor necrosis factor - α (TNF - α)， interleukin-6 (IL - 6)，interleukin-8 (IL-8)，transforming growth factor - β1 (TGF - β1) content and Smad3 expression were compared before and after treatment between the two groups. Results：After treatment， the sepsis symptom scores (Nausea and vomiting symptom scores were excluded) in the two groups were lower than those before treatment (P＜0.05)，and the sepsis symptom score in the study group was lower than that in the control group (P＜0.05). The ICU hospitalization and mechanical ventilation time in the study group were lower than those in the control group (P＜0.05). The 1-month follow-up results showed that there was no 28-day mortality case in the two groups. The total effective rate was 92.50% in the study group， higher than that of 75.00% in the control group (P＜0.05). After treatment， the PaO2 / FiO2 in the two groups was higher than that before treatment (P＜0.05)， and the PaO2 / FiO2 in the study group was higher than that in the control group (P＜0.05). After treatment， the Pa (A-a) O2 in the two groups was lower than that before treatment (P＜0.05)， and the Pa (A-a) O2 level in the study group was lower than that in the control group (P＜0.05). After treatment，the levels of TNF - α，IL-6 and IL-8 in serum in the two groups were lower than those before treatment (P＜0.05)，and the levels of TNF- α，IL-6 and IL-8 in serum in the study group were lower than those before treatment (P＜0.05). After treatment，the levels of TGF - β1 content and Smad3 protein expression in serum were lower than those before treatment (P＜ 0.05)，and the levels of TGF- β1 content and Smad3 protein expression in serum in the study group were lower than those in the control group (P＜0.05). Conclusion： Huatan Tongfu Prescription has a good curative effect on sepsis-associated lung injury，which can improve the levels of inflammation in the body and enhance prognosis. Its mechanism of action may be related to the inhibition of TGF-β1/Smad3 signaling pathway.