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To understand the impact of CO2-brine-rock interaction on formation properties and the differences between gas zone and water zone, dynamic and static experiments were conducted under gas reservoir conditions to imitate the process of CO2 injection and storage in gas reservoirs with aquifer. In this work, core plugs, rock debris and brine are taken from DF gas field, a giant gas reservoir with aquifer in the South Sea of China. Meanwhile, scan electron microscope (SEM), energy dispersive spectrum (EDS), X-ray diffraction (XRD) and flame atomic absorption spectrometry (FAAS) were also applied to analyze the mechanism of property alterations of brine and rock minerals due to CO2-brine-rock interaction. Results show that CO2-brine-rock interaction occurs in both gas zone and water zone since water evaporates into gas stream and CO2 dissolves into brine to form carbonic acid. CO2-brine-rock interaction can cause rock minerals dissolution and to fall from the matrix to form free particles suspending in pore space filled with fluids and flow along with them. It generally triggers sharp reduction of formation permeability and leads to negative impact on CO2 injectivity and storage. And the formation damage in gas zone is severer than that in water zone. Meanwhile, CO2-brine-rock interaction in good-quality reservoir in water zone can improve porosity and permeability to further enhance CO2 injectivity and storage capacity. Thus, dry CO2 should be preferentially injected into aquifer with good formation properties to weaken negative effect to ensure CO2 successful injection and storage in gas reservoirs with aquifer. This work also provides a reference for designing technical scheme of CO2 injection and storage in gas reservoirs with aquifer.