Invasive fungal disease (IFD) is a group of serious infectious diseases caused by fungi. In recent years, its incidence has shown an upward trend. Traditionally, the diagnostic criteria for IFD primarily target patients with neutropenia. However, in clinical practice, more and more IFD patients do not have neutropenia as their underlying disease. Instead, they are non-neutropenic patients with high-risk factors such as chronic obstructive pulmonary di-sease (COPD), severe viral pneumonia, and diabetes, etc. Their clinical features, imaging manifestations, laboratory tests, and diagnostic criteria are significantly different from those of neutropenic patients. This article comprehensively expounds the diagnostic criteria and their evolution for IFD in non-neutropenic patients, especially highligh-ting the differences from neutropenic patients, so as to provide a reference for the correct clinical diagnosis of IFD.