Abstract: Disclosed is a tumor vaccine based on tumor-derived microparticles (TMPs), and a preparation method and use thereof. The preparation method includes the following steps: 1, subjecting tumor cells to separation to obtain TMPs; 2, mixing the TMPs with 0.03 ?g/?l of a polyethyleneimine solution to allow a reaction for 10 min to 20 min, and washing to obtain PEI-modified TMPs (TMPs-PEI); and 3, mixing the TMP-PEI with 0.1 ?g/?l of a lipopolysaccharide solution to allow cross-linking for 15 min to 1 h to obtain the tumor vaccine based on TMPs (TMP-PEI-LPS). A nanomaterial prepared by conducting surface modification on the TMPs with an immunologic adjuvant can be disguised as a bacterial analog to promote the recognition of tumor antigens in vivo. Moreover, the TMPs can retain their immunostimulatory ability and reduce their toxicity by using a cross-linking agent coupled with the immunologic adjuvant.