The effects of spectral resolution, spectral calibration accuracy, surface reflectance, atmospheric profile, and radiation resolution on the CO2 column sensitivity for hyperspectral sounding were simulated by the infrared radiation transfer model MODTRAN5. In the meantime, sounding radiance variation index S changing with the gas content was defined. And the relationship of sounding sensitivity, spectral resolution, and signal-to-noise ratio (SNR) were comprehensively analyzed. Results can be taken as the reference for designing future hyperspectral IR sensors and developing hyperspectral retrieval algorithm. The results can provide an important reference for channel selection about CO2 column inversion and analysis about CO2 sounding sensitivity parameter.