The aim of the present study was to investigate the treatment of refractory Cryptococcus neoformans encephalitis with continuous administration of liposomal amphotericin B (AmB). Liposomal AmB was administered to a 28-year-old male by intravenous injection, with daily increasing dosages up to 150 mg per day and combined use of fluconazole (0.4 g per day) and oral flucytosine tablets (1.5 g per day). Following 5 months of treatment, C. neoformans could still be detected in the ink stain of cerebrospinal fluid, but the patient could not tolerate a further increase in the dosage of liposomal AmB. Instead, continuous intrathecal administration of AmB through tube drainage on the lumbar cistern was used. A total dosage of 28 mg liposomal AmB was administered to the patient over the course of 1 month. The effect of AmB administered by intravenous injection was not as great as expected and the patient's tolerance was not good. However, the patient recovered following treatment by continuous intrathecal administration of AmB through tube drainage on the lumbar cistern for 1 month. This case suggests that continuous intrathecal administration of liposomal AmB should be considered for clinical treatment of refractory cryptococcal encephalitis.