Purpose: Melittin (MPI) is a potential anticancer peptide due to its abilities of antitumor and immunomodulatory functions. Epigallocatechin-3-Ogallate (EGCG), a major extract of green tea, has shown great affinity for various types of biological molecules, especially for peptide/protein drugs. The aim of this study is to prepare a fluoro- nanoparticle (NP) formed by self-assembly of fluorinated EGCG (FEGCG) and MPI, and evaluate the effect of fluorine modification on MPI delivery and their synergistic antitumor effect.Methods: Characterization of FEGCG@MPI NPs was determined by dynamic light scattering (DLS) and transmission electron microscope (TEM). Biology functions of FEGCG@MPI NPs were detected by hemolysis effect, cytotoxicity, apoptosis, cellular uptake with confocal microscopy and flow cytometry. The protein expression levels of Bcl-2/Bax, IRF, STATT-1, P-STAT-1, and PD-L1 were determined via western blotting. A transwell assay and wound healing assay were used to detect the cell migration and invasion. The antitumor efficacy of FEGCG@MPI NPs was demonstrated in a subcutaneous tumor model.Results: Fluoro-nanoparticles could be formed by self-assembly of FEGCG and MPI, and fluorine modification on EGCG could ameliorate the side effect and delivery of MPI. The promoted therapeutics of FEGCG@MPI NPs could be achieved by regulating PD-L1 and apoptosis signaling, which might involve pathways of IRF, STAT-1/pSTAT-1, PD-L1, Bcl-2, and Baxin vitro. Moreover, FEGCG@MPI NPs could significantly inhibit the growth of tumorin vivo.Conclusions: FEGCG@MPI NPs may offer a potential platform and promising strategy in cancer therapy.