Cryptococcus neoformans (C. neoformans) is a yeast-like fungus, which can not only cause lung tissue infection, but also cause life-threatening meningoencephalitis. When humans are infected with C. neoformans, macrophages act as the first line of immune defense to quickly identify, phagocytose and destroy pathogens. The diffe-rent results of interactions between C. neoformans and macrophages will lead to different outcomes, understanding these mechanisms plays a key role in the prevention and treatment of cryptococcosis. This article reviews the intera-ction between C. neoformans and macrophages and the intrinsic molecular mechanism during infection, and provides theoretical basis and direction for vaccine development and immunotherapy of cryptococcosis.