The invention provides a preparation method of an intermediate of a steroidal drug with a 16-beta-methyl. In the method, a steroidal compound I is used as a starting material, and a steroidal compound II of the intermediate of the steroidal drug with the 16-beta-methyl can be prepared through epoxy reaction, ketal reaction, hydrogenation reaction, addition reaction and hydrolysis reaction for transformation of Position 3, Position 5, Position 6, Position 16, Position 17 and Position 20 or Position 5, Position 6, Position 16, Position 17 and Position 20. The steroidal compound II with the 16-beta-methyl is generally applied in preparation of the glucocorticoid drugs commonly used in clinical operation, such as betamethasone, betamethasone sodium phosphate, betamethasone acetate, clobetasol propionate, beclometasone dipropionate, betamethasone valerate and the like. In the formulas of the steroidal compound I and the steroidal compound II, R represents OH or OCOCH3, R1 represents OH, R2 represents CH3, and R3 represents CH3.