Fungal infections gradually lead to a high mortality rate due to difficulties in diagnosis, the limited number of antifungal drugs available, and the appearance of resistant isolates. Here, we developed a calcofluor white-cholesteryl hydrogen succinate conjugate (CFW-CHSc) as a novel nanomaterial that specifically binds to chitin chains in the cell wall. We showed that fluorescent-dye loaded CFW-CHSc-liposomes entered the cytoplasm of Candida albicans cells with increased efficacy. Voriconazole-loaded CFW-CHSc-liposomes displayed an increased antifungal activity against C. albicans yeast cells in an in vitro assay. Animal infection models and animal imaging analysis showed that fluorescent-dye loaded CFW-CHSc-liposomes maintained prolonged residence in rodent tissues. In mouse liver and kidney tissue, voriconazole-loaded CFW-CHSc-liposomes showed significantly enhanced antifungal activity when administered intravenously. Taken together, our studies confirm that CFW-CHSc increases the drug delivery efficacy of nanoparticles in vitro by interacting with chitin chains in the C. albicans cell wall. The fungi-targeting nanoparticles improve the drug delivery efficacy in vivo by enriching the nanoparticles at the site of fungal infection via the blood circulation system. Fungi-targeting nanomaterials have a promising future in the treatment of nosomycosis.