| To observe and discuss the therapeutic effect of Chaihu Guizhi Ganjiang Decoction in the treatment of gastroesophageal reflux disease (GERD) patients with liver depression and spleen deficiency syndrome, and its improvement on gastrointestinal function related indicators. Methods: 90 patients with GERD diagnosed by gastroscope in our hospital from March 2020 to March 2022 were selected, which were in line with the syndrome type of liver depression and spleen deficiency in traditional Chinese medicine. They were randomly divided into two groups by computer numerical table, with 45 patients in each group. The control group was treated with conventional quadruple therapy. The observation group was treated with Chaihu Guizhi Ganjiang Decoction on the basis of the medicine used in the control group for 12 weeks. The therapeutic effect of gastroscope was evaluated after observation and comparison of the two groups. The follow-up was half a year, The recurrence rate of the two groups was observed; The changes of TCM score, esophageal dynamics index, gastrointestinal and esophageal function index and DeMeester score were observed before and after treatment. Results: The scores of TCM, esophageal dynamics, gastrointestinal and esophageal function and DeMeester score in the two groups after treatment were significantly improved compared with those before treatment (P<0.05), and the improvement in the observation group was more significant (P<0.05); After 12 weeks of treatment,the efficacy rate of the observation group is 95.6%, which is more significant than that of the control group, 80.0% (X2=5.50,P<0.05); Follow up for 6 months showed that the recurrence rate of 2.2% in the observation group was significantly lower than that of 20.0% in the control group (X2=7.20,P=0.007). Conclusion: With the addition and subtraction of Chaihu Guizhi Ganjiang Decoction, the treatment effect of GERD patients with liver depression and spleen deficiency is better than that of western medicine alone. It can significantly improve the relevant TCM symptoms, regulate gastrointestinal and esophageal functions, improve esophageal motility, promote the prognosis, and reduce the recurrence rate, which is worthy of reasonable promotion.