Objective: To explore the effect of intervention guided by voice handicap index and reflux index in patients with thyroid cancer. Methods: A total of 108 patients undergoing thyroid cancer surgery in our hospital from January 2020 to January 2021 were selected and randomly divided into 2 groups, with 54 cases in each group. The control group underwent routine intervention, and the observation group underwent intervention guided by the voice handicap index and reflux index. The changes in voice acoustic value, voice handicap index, throat reflux symptom index, psychological elasticity level and quality of life were compared between the 2 groups after surgery. Results: The acoustic value of the observation group’s maximum voice and amplitude perturbation voice after operation was higher than that of the control group, and the fundamental frequency perturbation voice acoustic value was lower than that of the control group (P<0.05); the scores of the voice disorder index in the observation group were lower than those in the control group at 3 months after operation (P<0.05); the throat reflux index scores of the observation group were lower than those of the control group 3 months after the operation (P<0.05); the psychological elasticity scores of the observation group were higher than the control group 3 months after the operation (P<0.05); the quality of life scores of the observation group were higher than those of the control group 3 months after operation (P<0.05). Conclusion: Intervention guided by voice handicap index and reflux index can improve the acoustic level of voice in patients with thyroid cancer, reduce postoperative voice disorder and throat reflux, and improve the level of mental elasticity and quality of life.