The invention belongs to the technical field of medicines, in particular to Pt+si-GPX4(at)IONPs and FA/Pt+si-GPX4(at)IONPs nano-particles as well as a preparation method and an application thereof. According to the invention, three therapeutic drugs, i.e., cis-platinum, si-GPX4 and IONPs, are combined into a whole; glioma cell death is jointly induced from two aspects of cell apoptosis and ferroptosis; in addition, the FA-modified liposome is used for wrapping three medicines, namely cis-platinum, si-GPX4 and IONPs, the advantages of good targeting property and high biocompatibility are achieved, a very good treatment effect on glioma is achieved, the defects of a traditional single chemotherapy medicine are overcome, and a multi-target combined chemotherapy method for glioma cells is provided.