The existence of organic matters in naturally hydrate-bearing sediments would notably impact the CH4 extraction from reservoirs via CO2 swapping. In this work, the depressurization-assisted flue gas replacement was explored with artificial hydrate-bearing clay-silt sediments containing organic matter. The effect of organic matter type and content, depressurization moment and amplitude was systematically investigated. The results showed that the replacement was promoted at 5.0 wt% sulfonated lignin (SL) before depressurization, while it was inhibited at a lower SL content and this inhibition was weakened after depressurization. The CH4 replacement ratio and CO2 sequestration ratio increased as the fulvic acid (FA) content increased. For the organic matter-contained systems, the earlier depressurization moment was conducted, the higher CH4 recovery was obtained. The CH4 replacement ratio increased with the increase of depressurization amplitude, which reached 71.48 % in the 3.0 wt% FA system at the depressurization amplitude of 3.0 MPa. Aspen simulation revealed that the energy consumption was mainly caused by compression, there exist an optimum injection pressure of flue gas for the energy return on investment. The findings provide useful information for the depressurization-assisted flue gas replacement and would contribute to the actual NGH exploitation in the future.