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Background: Pulmonary Aspergillus has a high incidence and mortality rate, but is difficult to be diagnosed. It is mainly caused by Aspergillus fumigatus. Pulmonary Aspergillus caused by Aspergillus oryzae is rare. This case reports an 8-year-old male patient with acute lymphoblastic leukemia (ALL) who was found to have pulmonary Aspergillus oryzae infection by NGS of alveolar lavage fluid. Case Summary: The patient had ALL and received induction remission chemotherapy. During chemotherapy, the patient developed severe agranulocytosis and severe pneumonia. The treatment was performed accordingly. The second-generation sequencing of alveolar lavage fluid identified the pathogen as Aspergillus oryzae. After combined antifungal treatment with caspofungin and voriconazole, pneumonia was absorbed and improved. One week later, spontaneous fluid pneumothorax accompanied by massive hemoptysis occurred, and the patient received rescue therapy, which was successful. Finally, the patient recovered after pulmonary lobectomy and purulent moss stripping. Conclusion: Early diagnosis and treatment of pulmonary Aspergillosis are very important. Aspergillus oryzae infection has only rarely been reported in humans. Second-generation sequencing of alveolar lavage fluid is an accurate and effective detection method to assist diagnosis of microorganism infection. Combination of caspofungin and voriconazole is an effective method to treat severe Aspergillus pneumonia. [ABSTRACT FROM AUTHOR]