In the process of CO₂ storage, the cement sheath is the weakest link in the casing-cement sheath-formation system. Under the casing pressure, especially alternating pressure, the cement sheath has a great risk of interface debonding. The failure of cement sheath sealing integrity lead to CO₂ leakage from the micro-annulus to the surface, which seriously affects CO₂ storage. Based on the elastic-plastic mechanical analysis model of casing-cement sheath-formation system, the formation mechanism of interface micro-annular and corresponding preventive measures in whole well sections are studied with MATLAB simulation analysis. The results show that the failure of cement sheath sealing integrity is mainly related to the plastic strain accumulation caused by the cement sheath entering plasticity, whether in shallow or deep well sections, as long as the cement sheath enters plasticity, there is a risk of “interface stress inversion” under the multiple loading and unloading, by which lead the failure of cement sheath sealing integrity. The cement sheath should be firstly avoided from entering the plastic state to avoid the failure of cement sheath sealing integrity, that is, increasing the yield internal pressure of cement sheath. In shallow well section, cement sheath with low elastic modulus and high Poisson"s ratio can increase the yield internal pressure of cement sheath. In deep well section, reducing the elastic modulus of cement sheath can effectively improve the yield internal pressure of cement sheath when above the "critical range" of Poisson"s ratio, increasing the elastic modulus of cement sheath can improve the yield internal pressure of cement sheath when below the "critical range" of Poisson"s ratio. When the cement sheath has to enter the plastic state due to excessive casing pressure, the cement sheath with low elastic modulus and high Poisson"s ratio can reduce the residual stress of the cement sheath after unloading and delay the occurrence of "interface stress inversion".