The invention relates to a multi-layer thermal transfer ribbon and a manufacturing method thereof, and the multi-layer thermal transfer ribbon comprises a membranous base band, a heat-resistant printing ink layer and a heat transfer printing ink layer, wherein the heat-resistant printing ink layer is coated on one side of the base band, the heat transfer printing ink layer is coated on the other side of the base band, the heat transfer printing ink layer comprises a stripping printing ink layer and an adhesive printing ink layer, the stripping printing ink layer is directly coated on the surface of the base band, the adhesive printing ink layer is coated on the stripping printing ink layer, printing ink in the striping printing ink layer is hot-melting type printing ink, and the printing ink in the adhesive printing ink layer is the hot-melting type printing ink or solvent type printing ink. The heat transfer printing ink layer of the multi-layer mixed-based ribbon can be easily completely stripped off the base band, and the great adhesive ability is realized on a smooth medium; in addition, the multi-layer thermal transfer ribbon further has the advantages of high resolution, clear printing, anti-friction property, moisture resistance, chemical corrosion resistance, environment friendliness and the like.