Previously, determining the injection volume of liquid CO2 used to displace CH4 in coal seam boreholes has lacked scientific input, and has mostly been based on engineering experience and analogy. Here, one scientific method combining theoretical analysis, physical experimentation, and underground measurements was used to determine the reasonable injection volume for a single borehole along a coal seam when injecting liquid CO2 to displace CH4 within the coal seam. Therefore, the amount of CH4, ΔXCH4 , that needs to be displaced by injecting liquid CO2 in a single borehole was obtained by theoretical calculation, and the displacement ratio, β , of CH4 displaced by injecting liquid CO2 under different pressures was analyzed. An in-situ test was designed to obtain the relationship between the injection volume and the distribution of the CO2 content in coal seams located at different distances from the injection hole and the other two key parameters in the equation, such as the influence coefficient, η, of the distribution of the CO2 content in the coal seam and the effective diffusion radius, l0. Based on the relationship between ΔXCH4 , β , η and l0, the empirical equation for the reasonable injection volume of single hole is obtained, and the correction equation is obtained after considering the influence coefficient ξ of CO2 flow non-uniformity. The results showed that to displace CH4, 6.1–7.7 m3 is a reasonable liquid CO2 injection volume range within a single borehole along the bed in 3303 working face when ΔXCH4 is 0.75 m3 t−1, β is 0.0088–0.01, η is 0.275, l0 is 16 m and ξ is 0.155. This method provides a theoretical basis and scientific guidance for applying liquid CO2 injection technology to displace CH4 in coal seams.