Abstract: The purpose of this study is to develop a liposomal drug delivery system actively targeting Cryptococcus neoformans and explore its feasibility in therapy of cryptococcal infection. The specific fungibinding peptide was screened from 12-mer random phage display library, and linked to PEG-DSPE as the functional material of liposomes. The targeting capability of peptide-modified liposomes were investigated by fungi binding assay in vitro and fluorescence imaging in vivo. Itraconazole as a model drug were then encapsulated in the liposomes and were evaluated in pharmacodynamic test in vitro and for therapeutic effects against cryptococcal meningitis complicated with pulmonary cryptococcosis in vivo. The results showed that the peptide (sequence:NNHREPPDHRTS) could selectively recognize Cryptococcus and effectively mediate the corresponding liposomal formulation to accumulate in the infection site in vivo. This peptide-modified liposome has a small particle size (mean diameter of 88.25±2.43 nm) with a homogeneous distribution and high encapsulation efficiency (88.05±0.25%) of itraconazole. After intravenous administration, the pathogens were obviously eliminated in lung and brain, and the life-span of model mice were significantly prolonged, suggesting a promising potential of this cryptococcosis targeting strategy.