Objective To explore the clinical characteristics and risk factors of nosocomial invasive pulmonary mycosis(IPM) in patients with hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF). Methods Clinical data of HBV-ACLF patients who were admitted to a hospital between November 2013 and August 2019 were collected, according to whether patients had IPM, they were divided into HBV-ACLF nosocomial IPM group (study group) and HBV-ACLF non-nosocomial IPM group (control group), clinical characteristics, pathogenic bacteria and risk factors of nosocomial IPM were analyzed. Results A total of 119 patients were included in study, 50 in study group and 69 in control group. In study group, 50 patients all had cough and expectoration, 29 had fever, 12 had obvious chest tightness, shortness of breath and hypoxemia, 28 had moist rales through lung auscultation; chest CT of 50 patients showed changes in different degrees, positive rates of serum 1-3-β-D-glucan antigen and galactomannan antigen were 72.00% and 36.00% respectively. A total of 30 strains of fungi were isolated, the most common fungi were Candida albicans (43.33%) and Aspergillus spp. (33.33%), the 28-day mortality was 76.00%. Long-term use of broad-spectrum antimicrobial agents, decrease of absolute neutrophil count, invasive procedure, proportion of 28-day mortality, total bilirubin level, international standardized ratio, score in model for end-stage liver disease, and length of hospital stay in study group were all higher than those in control group (all P<0.05). Conclusion Clinical manifestations of HBV-ACLF patients with nosocomial IPM have no obvious specificity, the main infection fungus is Candida spp., which is related to the long-term use of broad-spectrum antimicrobial agents, decrease of absolute neutrophil count and invasive procedure, prognosis is poor.