The embodiments of the present disclosure provide a detachable anti-vibration sealing protection device for a pipe flange. The protection device includes a casing, wherein left and right end surfaces of the casing have through holes for the pipeline to pass through, and the casing has an accommodation cavity for placing the flange; a first shock absorption assembly for radial shock absorption of the flange; and a second shock absorption assembly which is installed in a one-to-one correspondence with the flange and is configured for axial shock absorption of the corresponding flange. The first shock absorption assembly and the second shock absorption assembly are installed in the accommodation cavity.