Abstract: A four-year-old non-neutered shorthair male cat presented to the doctor due to loss of appetite and lethargy, and medical history, clinical examination, hematological examination, imaging examination, cytological examination, ophthalmic examination and serum antigen agglutination test were used to carry out preliminary screening and diagnosis, and the treatment was performed based on the diagnosis results. The results showed that the cat was diagnosed as a systemic Cryptococcus infection, the primary site was frontal sinns and caused meningoencephalitis with related neurological symptoms. The cat recovered well after fluconazole treatment, and there was no recurrence within one year after treatment. The results suggested that the clinical diagnosis of feline cryptococcosis was difficult; after a systematic diagnosis was made, accurate and timely treatment would improve the prognosis of the disease.