The invention provides a protamine oligopeptide modified paclitaxel liposome and a preparation method thereof, and belongs to the technical field of pharmaceutical preparations. The protamine oligopeptide modified paclitaxel liposome provided by the invention comprises the following raw materials of protamine oligopeptide LMWP, paclitaxel, lecithin, cholesterol and glucose. The protamine oligopeptide LMWP is combined with a liposome embedding technology, the operation is simple and convenient, the obtained paclitaxel liposome is stable in property and high in bioavailability, the average particle size is about 124.43 nm and is smaller than that of a common paclitaxel liposome, the zeta potential is -40.6 mV, and the storage stability is good. The water solubility of the protamine oligopeptide modified paclitaxel liposome is improved, the content of the paclitaxel liposome in cells is also increased accordingly, the paclitaxel liposome has the effect of enhancing the drug effect, and protamine can obviously reduce the density of blood vessels in tumors and has the anti-tumor effect.