Invasive fungal infection (IFI) can be a lethal complication in systemic lupus erythematosus (SLE). The aim of this study was to determine the characteristics of hospitalized SLE patients with IFI, and identify the risk factors compared to SLE with other major infections or those with active disease alone. Data from 18 SLE in-patients with IFI at Shanghai Renji Hospital between January 2007 and January 2011 were collected by chart review. SLE patients with either active Mycobacterium tuberculosis (n = 19) or other bacterial infections (n = 17), or active SLE (n = 54) in the same period acted as controls. SLE in-patients with IFI (n = 11) from January 2002 to December 2006 was considered as a historical control group. The most frequent pathogens of SLE-IFI was Cryptococcus neoformans (n = 9, 50.0 %), followed by Aspergillus and Candida (both n = 3, 16.7 %). The infection sites included lung (n = 8, 44.4 %), central nervous system (n = 8, 44.4 %), and disseminated IFI (n = 2, 11.1 %). Three patients (16.7 %) died from IFI. Compared with other major infections, IFI patients were younger, with shorter SLE disease duration, lower C-reactive protein response, higher corticosteroids, and antibiotics exposure. Compared with active SLE, IFI patients had elevated alanine transaminase level, higher corticosteroids and antibiotics exposure. In multivariate analysis, the only significant risk factors for IFI were maximum prednisolone exposure ≥45 mg/day prior to infection or flare within 3 months (OR = 10.284, 95 %CI (2.877, 36.836)). Compared with the historical SLE-IFI patients, the short-term survival improved over time (63.6 % versus 83.3 %). SLE-IFI is a unique entity that characterized by certain aforementioned parameters compared with other major infections or disease flare in SLE. Familiar with the disease pattern along with appropriate antifungal treatment may lead to a better outcome in SLE-IFI patients.