The low recovery of oil from tight liquid-rich formations is still a major challenge for a tight reservoir. Thus, supercritical CO2 flooding was proposed as an immense potential recovery method for production improvement. While up to date, there have been few studies to account for the formation properties’ variation during the CO2 Enhanced Oil Recovery (EOR) process, especially investigation at the micro-scale. This work conducted a series of measurements to evaluate the rock mechanical change, mineral alteration and the pore structure properties’ variation through the supercritical CO2 (Sc-CO2) injection process. Corresponding to the time variation (0 days, 10 days, 20 days, 30 days and 40 days), the rock mechanical properties were analyzed properly through the nano-indentation test, and the mineralogical alterations were quantified through X-ray diffraction (XRD). In addition, pore structures of the samples were measured through the low-temperature N2 adsorption tests. The results showed that, after Sc-CO2 injection, Young’s modulus of the samples decreases. The nitrogen adsorption results demonstrated that, after the CO2 injection, the mesopore volume of the sample would change as well as the specific Brunauer–Emmett–Teller (BET) surface area which could be aroused from the chemical reactions between the CO2 and some authigenic minerals. XRD analysis results also indicated that mesopore were altered due to the chemical reaction between the injected Sc-CO2 and the minerals.