In order to study the effect of water-rock interaction on the mechanical and acoustic emission characteristics of coal gangue, we first prepared the hydro-chemical solution with reference to the composition of groundwater, then we selected coal gangue samples with similar sound velocity and density and immersed the samples into the chemical solution with different pH values for several days, dried the samples for sound velocity testing, and conducted the acoustic emission (AE) tests on the samples during the whole process of uniaxial compression. By tests, we obtained the time-varying laws of gangue mass density, sound velocity, and concentrations of the calcium and magnesium ion in the solution during gangue soaking and the time course curves of stress and acoustic emission characteristics of the soaked sample during uniaxial compression. The grey relational theory was applied to analyze the main factors influencing the uniaxial compressive strength and acoustic emission energy of the gangue from two aspects of water and rock. Based on the least square method, the three most significant factors were selected to establish the multiple regression models of the maximum acoustic emission energy and the uniaxial compressive strength of coal gangue samples, respectively. The study shows that for the coal rock samples soaked in chemical solution: (1) the initial pH value has a significant impact on the concentration of calcium and magnesium ions in the solution, which has reached the highest level in acid solution (Ca2+ concentration is 53 mmol/L-1 and Mg2+ concentration is 8 mmol/L-1); (2) the gangue soaked in neutral solution has the highest mass change ratio; (3) the sound velocity of coal gangue in the middle stage of soaking is significantly higher than that in the early stage of soaking, reaching 1.45 times; (4) the acoustic emission energy count of coal gangue samples in the uniaxial compression process is obviously stage managed; (5) Based on the least square method, the multiple regression models of the compressive strength and the maximum acoustic emission energy in the uniaxial compression test of coal gangue samples were established, and the correlation coefficients reached 0.89 and 0.98, respectively. The research can provide some theoretical reference for the mechanical analysis of coal samples and other subsequent studies also have important engineering significance for ensuring the safety of coal gangue engineering after water-rock interaction in real environments.