Abstract: To solve the problems of low replacement efficiency of natural gas hydrates by carbon dioxide injection and difficulty in obtaining the replacement reaction rate constant at any temperature and pressure, hydrate samples with saturation of about 80% were synthesized indoors in porous medium, and replacement experiments for methane hydrate via carbon dioxide injection and replacement were conducted by constant volume and huff and puff. Chemical composition of gas sample and hydrate replacement ratio were determined by chromatographic analysis, and replacement driving forces were calculated by chemical thermodynamics theory, the calculation equation of the replacement reaction rate constant was established by using data inversion and multiple linear regression methods. Research has shown that the replacement ratio of huff and puff replacement is increased by 45% compared to constant volume replacement. The replacement reaction rate constant exhibits a binary linear quantitative relationship with temperature and pressure, and the error between the replacement reaction rate from the quantitative relationship and that from the experiments is less than 5%, which achieved accurate calculation of the replacement reaction rate constant at any temperature and pressure.