We report the case of an adolescent with severe primary ciliary dyskinesia (PCD) phenotype associated with a rare genotype. His clinical condition deteriorated, with daily cough and breathlessness, hypoxemia, and lung function decline. Despite being started on home noninvasive ventilation (NIV), the symptoms progressed to dyspnea at rest and thoracic pain. High-flow nasal cannula (HFNC) was started during the daytime as an adjuvant to NIV, and he was started on regular oral opioids for pain and dyspnea control. There was a clear improvement in comfort and dyspnea and breathing work relief. Additionally, better exercise tolerance was also noted. He is currently on the lung transplant waiting list. We aim to emphasize the benefits of HFNC as an add-on therapy for the management of chronic breathlessness since our patient experienced an improvement in breathing and exercise tolerance. However, there is a paucity of studies regarding domiciliary HFNC, particularly in pediatric age. Therefore, further studies are needed to achieve optimal and personalized care. Close monitoring and frequent reassessment in a specialized center are key to adequate management.