CO2 sequestration in deep unminable coal seams is currently identified as a research hot spot to reduce CO2 emissions, due to the potential large-scale storage capacity and complicated physical and chemical reactions, especially for supercritical CO2 (scCO(2)). Hitherto, the interaction mechanisms between scCO(2) and coal mass in situ conditions are still unclear. Therefore, the main objective of this study is to fully address the coupling effects of scCO(2) sequestration on coal mass and provide a comprehensive evaluation of the interrelation of these variations. Five cycles of helium and scCO(2) injection were replicated on a subbituminous coal sample to investigate the permeability variation with scCO(2) saturation time. Meanwhile, gas chromatography-mass spectrometry (GC-MS), gas chromatography (GC), Fourier transform infrared spectroscopy (FTIR), proximate analysis, and low-pressure-temperature nitrogen (N-2) isotherm analyses were employed to characterize the transformation in coal mass. The test result shows the following: (1) scCO(2) tended to mobilize a higher proportion of aliphatics than aromatics, and the concentration of the yielded hydrocarbons decreased with CO2 saturation time. (2) Carbonate and silicate cemented minerals were partly dissolved due to the formation of an acidic solution containing H2CO3. (3) The hydrocarbon extraction and mineral dissolution resulted in the corresponding FTIR absorbance bands being weakened and the volatile matter content and the ash content being decreased by approximately 15 and 26%, respectively. (4) The coal pore volume and the Brunauer-Emmett-Teller (BET) surface area decreased by approximately 24 and 12%, respectively. (5) Due to CO2 adsorption and the reduction of Young's modulus with saturation time, the volumetric strain increased from 0.23 to 3.26%, which led to coal permeability decrease from 0.042 to 0.029 mdarcy. After analysis of the interrelation of these variations, the interaction mechanisms between scCO(2) and coal mass in situ conditions were described and an overall negative effect on coal permeability was found.