The research on the micro-mechanism and efficiency of CH4-CO2 replacement from natural gas hydrates are investigated in this work by a series of experiments with pure CO2, CO2/N-2, CO2/H-2 and CO2/He gas mixtures under 4.5 MPa and 274.0 K. In situ Raman and FTIR are employed to determine the micro structures and components of the hydrates. The results indicate the small gas molecules help to increase the rate of CH4-CO2 replacement, and adding H-2 or N-2 into the system has great effect on enhancing the CH4 exploitation efficiency as H-2 or N-2 molecules can weaken the van der Waals forces between CH4 molecule and hydrate crystal cave and further lead to the deformation of the hydrate cavities in the process. The Raman spectra illustrate no hydrate structure change exists in the replacement process, and the FTIR spectra illustrate the replacement can happen in both large and small cavities. The mechanism of CH4-CO2 replacement in the hydrate can be descripted as the introduction of CO2 breaks the balance of two phases of CH4 and CH4 hydrate, resulting in the deformation or dissociation of the CH4 hydrate, and finally forming CO2 hydrates with free water by the hydrate structure reconstitution.