The objective of this research is to study the replacement efficiency of methane hydrate with CO2, which is an important index to describe the use of CO2 for this application and to evaluate its economic benefits. An experimental study was designed to simulate the replacement of methane hydrate with CO2 in a low permeability, porous medium, and analyze the influence of different factors such as injection rate (0.5-1.5 ml/min), total amount (1.8-5.4 L), temperature (275-279 K) and pressure (3-5 MPa) by controlling these variables. The results indicated that the total amount at injection and the temperature had relatively significant impacts on the replacement efficiency. The CO2 injection rate and pressure primarily affected the CH4 production rate, rather than the total amount produced. The injection temperature and pressure should be comprehensively optimized for improved economic benefits. The ultimate replacement efficiency ranged from 22.9% to 44.6%, and the ultimate production ratio ranged from 3.35% to 13%, confirming the necessity of a comprehensive optimization of the influencing factors and implying that most of the large cavities had not yet been occupied by CO2.