The invention belongs to the field of pharmaceutic preparations, and relates to a targeted ligand-PEG (
polyethylene glycol)-
cholesterol / 
tocopherol derivative, and a preparation method and an application of the derivative, in particular to an application of the derivative in a composite mechanism mediate 
tumor targeted drug delivery system. According to the derivative, the preparation method and the application, a 
drug delivery system consisting of the targeted ligand-PEG-
cholesterol / 
tocopherol derivative with a targeting function, a 
long circulating function and a pH (power of 
hydrogen) sensitive function as a functional material, a cation 
liposome and a 
drug can simultaneously carry anticancer polypeptide and 
gene / 
chemotherapy drugs. According to the 
system, different drugs are jointly entrapped into the lipid 
nano drug delivery system and delivered into a targeted 
cell by utilizing a physicochemical property difference between components or by in-vivo specific targeted recognition, 
signal conduction blocking and pH triggering PEG chain breaking charge reversion methods, so that a targeted tumor 
therapeutic effect is improved. According to the derivative, the preparation method and the application, the advantages of the 
system in directional delivery, co-delivery and the like are proved by in-vivo and in-vitro activity evaluation, the anticancer activity is improved significantly, and definite synergic therapeutic and 
immunity effects are provided.