Objective To observe the effect of gastric acid inhibitor on postoperative clinical symptoms and quality of life of patients with vocal cord leukoplakia, and to explore the important role of gastric acid inhibitors in the treatment of vocal cord leukoplakia.Methods Fifty patients with vocal cord leukoplakia accompanied by laryngopharyngeal reflux admitted to the Department of Otolaryngology of Peking University Shenzhen Hospital from December 2015 to December 2018 were enrolled. According to the random number table, 50 patients were randomly divided into study group (with esomeprazole treatment) and control group (without esomeprazole treatment) with 25 cases in each group. Eight weeks after surgery, the recurrence and cancerization, scores of Reflux Symptom Index (RSI), Reflux Finding Score (RFS), Voice Handicap Index-10 (VHI-10) and 36-Item Short Form Health Survey (SF-36), voice function (amplitude perturbation, noise to harmonic ratio, fundamental frequency perturbation), and electronic laryngoscopy (the symmetry of vocal cord vibration and mucosal wave) were observed.Results There was no significant difference in recurrence rate and cancerization rate between the two groups after treatment (P > 0.05) . The differences in scores of RSI and RFS before and after the treatment were higher in the study group than those in the control group (P < 0.05). Compared with the control group, the differences in fundamental frequency perturbation, amplitude perturbation, noise to harmonic ratio and mucosal wave before and after the treatment were greater in the study group (P <0.05). Besides, the differences in scores of general health, physical functioning, bodily pain, vitality, social functioning and mental health before and after the treatment were lower in the study group that those in the control group (P <0.05).Conclusions The gastric acid inhibitor esomeprazole can relieve the reflux symptoms of patients with vocal cord leukoplakia accompanied by laryngopharyngeal reflux, improve their voice function and vocal cord function, and enhance their quality of life.