Objective: To discuss the effect of gastroesophageal reflux cough (GERC) treated with Jiawei Sini decoction. Methods: Sixty-eight patients with GERC from January 2014 to December 2015 were randomly divided into an experiment group and a control group, each with 34 patients. The control group were treated with omeprazole enteric-coated tablets and motilium tablet, while the experiment group were treated with Jiawei Sini decoction. The clinical effects, the cough symptom scores and the adverse effects before and after treatments were observed in the two groups. The levels of IL-8 and SP were detected before and after treatments. Leicester Cough Questionnaire (LCQ) were used to evaluate the quality of life of patients. Results: The cough symptom scores was 1.08±0.69 after treatments in the experiment group, which was lower than 2.38±0.86 in the control group; the LCQ scores was 18.98±3.24 after treatments in the experiment group, which was more than 15.42±2.73 in the control group, the differences were statistically significant (P<0.05). The total effective rate in the experiment group was 94.12%, which was more than 76.43% in the control group, the difference was statistically significant (P<0.05). The levels of IL-8 and SP were (24.58±8.79) pg/mL and (4.89±1.64) pg/mL after treatments in the experiment group, which was lower than (36.19±12.53) pg/mL and (9.78±3.42) pg/mL in the control group, the differences were statistically significant (P<0.05). Conclusion: Patients with GERC treated with Jiawei Sini decoction can improve symptom of cough, enhance quality of life, and decrease the levels of IL-8 and SP, which is worthy of clinical use.