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Background Deep fungal infections (DFIs) represent a significant and growing threat to hospitalized patients, contributing to substantial morbidity and mortality worldwide. The healthcare landscape has undergone notable changes in recent years, particularly with the impact of the COVID-19 pandemic, which has altered host immunity and care pathways, potentially influencing the epidemiology of DFIs. Objective This study aimed to delineate the clinical characteristics, mycological profiles, risk factors of deep fungal infections, and to evaluate factors associated with mortality among inpatients in a general hospital in southwestern China from 2020 to 2024. Methods This was a retrospective analysis of 886,056 patients in the hospital from 2020 to 2024, including the epidemiological characteristics, treatment, and prognosis of deep fungal infections. Results A total of 462 cases (0.052%) with deep fungal infections were identified, accounting for 0.052% of the total number of hospitalizations. The incidence of deep fungal infections in the hospital showed an increasing trend from 2020 to 2024. Compared with previous studies, Candida remained the predominant pathogen (84.20%), with increased proportions of Aspergillus (13.90%) and Cryptococcus (6.71%). A new case of Mucor infection (0.22%) was reported. The respiratory tract remains the most common site of infection (88.60%). In terms of treatment, most patients received azole therapy (88.30%), with those treated with echinocandins showing significantly higher survival rates ( P = 0.033). Multiple logistic regression analyses revealed that mixed infections, hematologic diseases, and biological agents were significant risk factors for poor prognosis (all P < 0.05). Conclusions Compared with earlier research (2015–2019), the number of deep fungal infection cases from 2020 to 2024 has shown a significant and sustained increase. Moreover, the threat posed by Aspergillus and Cryptococcus has increased. Although clinical data remain limited, these findings provide valuable insights for the prevention, diagnosis, and treatment of deep fungal infections. Compared with earlier research (2015–2019), the number of deep fungal infection cases from 2020 to 2024 has shown a significant and sustained increase. Moreover, the threat posed by Aspergillus and Cryptococcus has increased. Although clinical data remain limited, these findings provide valuable insights for the prevention, diagnosis, and treatment of deep fungal infections.