The invention discloses a novel preparation method of a carfilzomib key intermediate. L-leucine is taken as an original raw material, two reactive hydrogen on an amino group are protected, a chemical compound V is prepared and subjected to Weinreb amidation, a chemical compound IV is prepared, IV and 2-allyl magnesium bromide have a reaction, a chemical compound III is prepared and has an epoxidation reaction, a chemical compound II is prepared and subjected to deamination protection, and a chemical compound I is prepared. The invention further discloses intermediate chemical compounds II, III, IV and V of carfilzomib. The preparation method is simple to operate, the total yield is high, the cost is low, the selectivity is high, and the preparation method is suitable for industrial production.