Abstract: To clarify the influence of core wettability on the seepage process during the CO₂ saline aquifer storage, this paper studies the influence of wettability change in the saline aquifer on the seepage process based on the pore-level seepage model combined with nuclear magnetic resonance (NMR) technology, providing theoretical support for revealing the two-phase seepage law under the effect of wettability. Firstly, the saturation parameters during the seepage process are measured by NMR technology in this paper, and the quadratic function coupling relationship between wettability and brine saturation is quantitatively analyzed. Later, based on the level set method at the two-dimensional level, by setting wettability as different wetting levels and spatial position functions, the influence of different wettability of the reservoir in displacing brine in the porous medium by CO₂ on the seepage process is simulated. It was found that based on the functional coupling relationship between nuclear magnetic resonance longitudinal relaxation time (T₁) and transverse relaxation time (T₂) and saline water saturation (S), the core wettability changes during CO₂ displacement of saline water could be well characterized. Based on the pore-scale seepage model representing the isotropy of wettability at the pore scale, it was discovered that when the core wettability was in extreme conditions, such as strongly hydrophilic (θ = 0°), neutrally wetted (θ = 90°), or strongly hydrophobic (θ = 180°), the residual water saturation was lower and the displacement effect was better. For anisotropic wettability, the displacement process was more complex, and its influence on relative permeability and residual saline water saturation varied. Especially, different wettability manifestations at the inlet and outlet ends would directly affect the two-phase seepage process. When the inlet end was more hydrophilic and the outlet end was more hydrophobic, the saline water seepage velocity was faster; this might be due to the anisotropic wettability causing the uneven distribution of seepage behavior, thereby resulting in spatial and temporal differences in seepage rate and displacement efficiency; it can be seen that the physical characteristics of the seepage channel have a significant influence on the seepage process. Future research needs to focus on the different effects at time scales in addition to the associated changes at spatial scales in the saline aquifer.