The invention relates to a sealing device for a filter cartridge opening of a horizontal natural gas separating filter. The horizontal natural gas separating filter comprises a filter cartridge barrel and a barrel cover, wherein the filter cartridge barrel is horizontally arranged, the filter cartridge opening is formed at one end of the filter cartridge barrel facing to the barrel cover, and the barrel cover is in sealing fit with the filter cartridge opening. The sealing device for the filter cartridge opening comprises a filter cartridge opening sealing stepped chamber, limiting blocks for latch blocks, latch blocks and a decompression mechanism, wherein a sealing ring slot is arranged on a bottom wall of the stepped chamber, and a sealing ring is arranged in the sealing ring slot; the limiting blocks for latch blocks are parallel to the bottom wall of the stepped chamber, and a latch block avoiding chamber is formed by a space between every two adjacent limiting blocks for latch blocks; the latch blocks are formed on the peripheral edges of the barrel cover; the decompression mechanism is arranged on one side of the barrel cover back to the filter cartridge barrel; and when the latch blocks are aligned with the latch block avoiding chamber and enter the filter cartridge opening sealing stepped chamber and the barrel cover is rotated for corresponding to the latch blocks to the area between the limiting blocks for latch blocks and the bottom wall of the stepped chamber, the barrel cover and the filter cartridge opening are sealed. The sealing is reliable and the safety is guaranteed.