Objective To investigate the clinical features of interstitial lung disease (ILD) complicated with severe Pneumocystis pneumonia (PCP). Methods The patients with interstitial lung disease complicated with severe Pneumocystis pneumonia who were admitted to the Respiratory Intensive Care Unit (RICU) of the Department of Respiratory and Critical Care Medicine, Nanjing Drum Tower Hospital from September 2017 to June 2022 were retrospectively analyzed. Laboratory examinations, imaging features, complications and mortality data were used to analyze the clinical characteristics and prognosis of these patients. Results A total of 17 patients admitted to the RICU were finally enrolled in this study. 16 of the 17 patients had a history of corticoids therapy, and none of the 17 patients had received prophylaxis before the onset of PCP; 58.8% (10/17) of them were ILD secondary to connective tissue disease, and 41.2% (7/17) were idiopathic ILD; all patients were tested positive for P. jirovecii with polymerase chain reaction and/or next-generation metagenomic sequencing in sputum, bronchoalveolar lavage fluid or serum; all patients developed respiratory failure (oxygenation index: 146.8±66.4 mm Hg) after onset; within 24 hours of admission, the pneumonia severity index score was 91.9±20.1 and the Acute Physiology and Chronic Health Evaluation Ⅱ score was 16.1±3.0; imaging findings showed diffuse ground-glass opacity in both lungs on the basis of the original ILD; all patients were treated with trimethoprim-sulfamethoxazole (TMP-SMX) and corticoids, 52.9% (9/17) patients were treated with TMP-SMX + caspofungin + clindamycin; 70.6% (12/17) patients were treated with mechanical ventilation; 76.5% (13/17) patients during hospitalization complicated bacterial infection, 9 cases (52.9%) had viral infection. The 28-day mortality was 64.7% (11/17), and the 90-day mortality was 82.4% (14/17), as of telephone follow-up (July 2022) the overall mortality was 88.2% (15/17). Conclusions ILD patients with severe PCP are progressing rapidly. The clinical manifestations are severe which are the same as acute exacerbation of ILD, with poor prognosis.