Brain nocardiosis is a serious opportunistic infection with high mortality. It exists more common in the immunocompromised hosts than the immunocompetent patients. Trimethoprim-sulfamethoxazole (TMP-SMZ) has been mostly considered as the choice of the medical treatment. Linezolid is also newly found to be effective to avoid the invasive surgery. The authors reported a case of patient with multifoci nocardial brain abscesses who failed with the combination of linezolid and TMP-SMZ alone but recovered with the surgery intervention and sequential antibiotics for 2 years. The patient lived a high quality life without recurrence and complications during the 30 months follow-up.Through the literature review, we recommend earlier stereotactic aspiration for diagnosis, combination with surgery intervention and prolonged anti-infection therapy would improve the prognosis.