Considering the complexity of optimizing well spacing with component numerical simulation，and the insufficiency of capturing reservoir heterogeneity and oil viscosity changing with space in CO2 flooding with conventional well spacing calculation methods，through a large number of experiments，the relationship between the threshold pressure gradient（TPG）and the permeability of low-permeability reservoir in Shengli Oilfield is obtained by regression. Based on the non-Darcy theory and considering the reservoir heterogeneity，reduced viscosity of crude oil by CO2 flooding，convection，diffusion and adsorption，a mathematical model of injector-producer pressure difference of line well pattern in CO2 miscible flooding is established，and methods to determine the critical flow well spacing and the reasonable production well spacing are proposed. Taking a low-permeability reservoir in Shengli Oilfield as an example，the critical flow well spacing for CO2 miscible flooding is calculated. The results indicate that when the permeability increases to a certain value，TPG stably decreases with the increase of permeability. When the apparent permeability decreases to a certain value，TPG sharply increases with the decrease of permeability. For the low-permeability reservoirs in Shengli Oilfield，with the increase of injector-producer pressure difference，the reasonable production well spacing gradually increases，and the calculated reasonable production well spacing is consistent with the actual injector-producer well spacing，which verifies the reliability of the calculation method in this paper.