Objective To analyze the risk factors of invasive pulmonary aspergillosis (IPA) in patients with interstitial pneumonia. Methods The clinical data of 770 cases of interstitial pneumonia admitted between December 2010 and August 2015 were collected. Among them, 46 cases were combined with IPA and 724 cases were not ombined with IPA. The clinical data was analyzed to explore the risk factors of IPA in patients with interstitial pneumonia. Results Univariate analysis showed that in the aspects of age (t=3.348, P=0.001), serum albumin level (t=8.381, P < 001), broad-spectrum antibiotic used within 3 months (χ2=87.157, P < 001), long-term administration of glucocorticoid (χ2=57.462, P < 001), long-term administration of immunosuppressive agents (χ2=31.715, P < 001), imaging in UIP type (χ2=20.632, P < 001), diabetes mellitus (χ2=9.737, P=0.002) and heart failure (χ2=9.300, P=0.002), there were significant differences between two groups. After multivariate logistic regression analysis, broad-spectrum antibiotic used within 3 months (OR=4.773, P < 001), long-term administration of glucocorticoid (OR=9.195, P < 001), long-term administration of immunosuppressive agents (OR=2.662, P=0.046), imaging in UIP type (OR=5.725, P < 001), and diabetes mellitus (OR=3.847, P=0.003) were found to be the risk factors of IPA in patients with interstitial pneumonia. Serum albumin level was negatively correlated with the occurrence of IPA in patients with interstitial pneumonia. Conclusions Various factors contribute to the occurrence of IPA in patients with interstitial pneumonia. Miscellaneous appropriate measures should be taken to reduce the incidence of IPA.