The invention relates to a core-shell type nano medical granule targeting to tumor cells. The core-shell type nano medical granule comprises an inner hydrophobic polymer with chemotherapeutics medicines and epigenetics medicines in an adsorbing manner, a single-layer lipid molecule layer wrapping the inner hydrophobic core, and an hydrophilic outer shell targeting to the tumor cells. The invention further relates to a preparation method of the core-shell type nano medical granule and the application of the core-shell type nano medical granule to preparing anti-tumor medicines. The core-shell type nano medical granule combines the nano wrapping, the chemotherapeutics medicines and the epigenetics medicines, thereby having the advantages of improving the medicine delivery targeting, improving the sensitivity of the tumor cells to the chemotherapeutics medicines, suppressing the medicine resistance of the tumor cells, and the like.