In patients with symptomatic atrial fibrillation refractory to optimal medical therapy, atrioventricular node ablation followed by permanent pacemaker implantation is an effective treatment option. A 66-year-old woman with symptomatic persistent atrial fibrillation refractory to multiple ablation procedures was referred to our institution. After optimal drug therapy, the patient still had obvious symptoms. Sequential His-Purkinje conduction system pacing and atrioventricular node ablation were performed. Left bundle branch pacing was used as a backup pacing method if thresholds of His bundle pacing were too high or loss of His bundle capture occurred in the follow-up. At the 6-month follow-up, the European Heart Rhythm Association classification for AF was improved, the score of the Atrial Fibrillation Effect on Quality of Life was enhanced, and the 6-Minute Walk Test was ameliorated. The present case was subjected to His-Purkinje conduction system pacing in combination with atrioventricular node ablation as treatment for a symptomatic persistent atrial fibrillation refractory to multiple ablation procedures, and this procedure alleviated symptoms and improved the quality of life in a short-term follow-up.