Polydopamine nanoparticles (PDA NPs) were prepared via dopamine self-polymerization; then, tumor cell lysate (TCL) was covalently attached onto the PDA NPs. The TCL loading capacity was 480 μg per mg of PDA NPs, and the resulting TCL@PDA NPs (241.9 nm) had perfect storage stability and negligible cytotoxicity against APCs. Tumor-bearing mice vaccinated with TCL@PDA NPs experienced significant delay in tumor progression due to the sufficient amount of CTLs and M1-type TAM as well as the deficient number of immunosuppression-related cells in the tumor tissues. Furthermore, empty PDA NPs had the ability to modulate DC maturation and delayed the development of tumors by facilitating the production of activated T cells and decreasing the subpopulation of MDSCs within the tumor microenvironment. Overall, these PDA NPs are expected to be a promising candidate for application as antigen delivery carriers because of their facile antigen loading method as well as their simple and rapid preparation process.