Objective To elucidate the clinical features of patients with non-HIV-infected pulmonary cryptococcosis, and provide a basis for early clinical identification, standardized diagnosis and treatment. Methods Clinical data of 80 patients with non-HIV-infected pulmonary cryptococcosis diagnosed in Beijing Chest Hospital from January 2018 to July 2025 were retrospectively analyzed, including demographic characteristics, clinical manifestations, laboratory examinations, pulmonary imaging findings, treatment and prognosis. Results Among the 80 patients, males accounted for the majority (66.3%). Common clinical manifestations included cough (22.5%), expectoration (12.5%) and fever (10.0%). Laboratory tests showed that the positive rate of serum cryptococcal antigen was 32.8%, and the patients with blood type O had a higher infection rate (42.5%). Pulmonary function testing revealed abnormalities in a subset of patients (30%), primarily manifesting as small airway dysfunction. Pathologically, both Grocott's methenamine silver (GMS) and periodic acid-Schiff (PAS) stains were found to effectively demonstrate Cryptococcus organisms in this study. Imaging findings were mainly characterized by pulmonary nodules/masses (70.0%) and patchy infiltrates (20.0%). More than half of the patients presented with involvement of a unilateral lung or the lower lungs. Cavitary lesions were present in 32 patients (40%). Univariate logistic regression analysis indicated that pulmonary opacities, cryptococcal antigen positivity, and AB blood type were potentially associated with cavity formation (P<0.05). Subsequent multivariate analysis identified positive cryptococcal antigen (P=0.001) and AB blood type (P=0.024) as independent risk factors for pulmonary cavitation. The patients with cavitary lesions had longer hospital stays. The overall effective rate of fluconazole treatment in the non-HIV-infected pulmonary cryptococcosis patients was 93.2%, indicating a generally favorable prognosis. However, prolonged hospitalization was significantly associated with poorer pulmonary function (P=0.037) and the presence of pulmonary cavities (P=0.017). Significant differences were observed between patients who did and did not receive antifungal therapy in several clinical parameters: clinical symptoms (P<0.001), pulmonary opacities (P<0.001), serum cryptococcal capsular antigen titer (P=0.013), absolute CD4 count (P=0.031), absolute neutrophil count (P=0.040), and C-reactive protein level (P=0.001). The effective rate of fluconazole treatment was 93.2%, and most patients had a favorable prognosis. Conclusions Pulmonary cryptococcosis in non-HIV-infected patients lacks specific clinical manifestations and is radiographically characterized by nodular masses and cavitations. The presence of cavitary lesions and pulmonary dysfunction suggests a prolonged treatment course. While prognosis following fluconazole therapy is generally favorable, clinical symptoms, radiographic findings, cryptococcal antigen titers, absolute CD4 count, absolute neutrophil count, and C-reactive protein levels may influence the selection of antifungal therapy. Clinicians should raise awareness of this disease, especially distinguishing it from malignant tumors such as lung cancer.