Sympathetic overactivity plays a crucial role in the genesis and aggravation of arterial hypertension in patients with Autosomal Dominant Polycystic Kidney Disease (ADPKD). Renal denervation has been shown to be effective and safe in reducing blood pressure (BP) in patients with treatment-resistant hypertension, even with chronic kidney disease (CKD). However, there are no cases in hypertensive patients with ADPKD. We report the exceptional case of a woman with stage 4 CKD secondary to ADPKD and uncontrolled treatment-resistant hypertension. Because of the ineffectiveness of all pharmacological and surgical therapeutic strategies, including the uninephrectomy, renal denervation by radiofrequency ablation of the renal artery was performed. The patient decreased the requirement of antihypertensive medication and the BP showed a remarkable reduction, that resulted stable 12 months after the procedure.