The invention discloses a synthesis method of 16α, 17α-epoxy-4-pregnene-3, 20-dione. The process steps are: 10.0 parts of oxygen bridge, 70-80 parts of n-heptane and 35-40 parts of Mix 6-7 parts of cyclohexanone, heat and stir with water; after cooling down, add aluminum isopropoxide catalyst, reflux vigorously for 4 hours, cool down; add 6-7 parts of 30% NaOH solution dropwise, reflux for 20 minutes, add 2 % NaOH solution 20-25 parts, reflux for 30min, and remove alkaline water; then add 1% NaOH solution 20-25 parts, distill until no oil drops, suction filter, wash, dry; then dissolve with absolute ethanol, Reflux, freezing, suction filtration, Dewas oxide. The consumption of solvent, oxidant and catalyst of the present invention is less, only needs twice alkali washing, has simplified technology, has reduced production cost, and the content of Wo Shi oxidation reactant can reach 98.2%, and productive rate is more than 80%; The use of toluene reduces environmental pollution.