This study observed the efficacy of Huazuojiedu Tongluo Prescription in the treatment of patients with gastric precancerous lesions of turbid toxin accumulating in the stomach and explored its possible mechanism.Methods:A total of 70 patients with gastric precancerous lesions of turbid toxin accumulating in the stomach admitted to the Spleen and Stomach Disease Department of Hebei Hospital of Traditional Chinese Medicine from March 2017 to April 2019 were selected，and they were randomly divided into observation group and control group，with 35 cases in each group.The observation group was treated with Huazuojiedu Tongluo Prescription，and the control group orally took four Weifuchun Tablets three times a day.Both groups were treated for six months.The expression of the key factors of the sonic hedgehog(Shh) signaling pathway，such as glioma-associated oncogene 1(Gli1)，suppressor of fused(SUFU)，and Cyclin D1，were detected by immunohistochemistry and western blot before and after treatment，and the safety indexes of the two groups during treatment were observed.The efficacy in terms of traditional Chinese medicine(TCM) syndrome，gastroscopy，and pathology were compared between the two groups.Results:The total effective rate of TCM syndrome，gastroscopy，and pathology in the observation group was higher than that in the control group(all P<0.05).Immunohistochemical staining of Gli1，SUFU，and CyclinD1 showed brown-yellow granules.Before treatment，there was no statistical significance in the protein expression(density value) of Gli1，SUFU，and CyclinD1 in gastric mucosa between the two groups(all P>0.05).After treatment，the protein expressions of Gli1 and CyclinD1 in gastric mucosa of the two groups were decreased，while the protein expressions of SUFU were increased，with statistical significance(all P<0.05).The above indexes in the observation group were significantly changed compared with the control group(all P<0.05).The western blot test results showed that before treatment，there were no significant differences in the expression of Gli1，SUFU，and CyclinD1 in gastric mucosa between the two groups(all P>0.05).After treatment，the protein expressions of Gli1 and CyclinD1 in gastric mucosa of the two groups were decreased，and the protein expressions of SUFU were increased，with statistical significance(all P<0.05).The above indexes in the observation group were significantly changed compared with the control group(all P<0.05).No adverse reactions occurred in the two groups during the medication，and no obvious abnormalities were found in the blood routine，urine routine，stool routine，liver and kidney functions，and electrocardiogram.Conclusion:The efficacy of Huazuojiedu Tongluo Prescription in the treatment of patients with gastric precancerous lesions of turbid toxin accumulating in the stomach is better than that of Weifuchun Tablets，and its mechanism may be related to the regulation of the key factor expression in the Shh signaling pathway，such as Gli1，SUFU，and CyclinD1.