To provide essential data for the separation of diethoxymethane and system water using mesityl oxide as the extractant, in this paper, the liquid-liquid equilibrium data of the ternary system of ‘mesityl oxide + diethoxymethane + water’ was measured at 303.2 K, 313.2 K and 323 K under normal pressure. The experimental results showed that partition coefficient and separation factor were both larger than 1, indicating that diethoxymethane and water could be well separated with mesityl oxide. The linear correlation coefficient of Bachman and Hand equation was larger than 0.99, indicating that our experimental data has good reliability. At the same time, the binary interaction parameters of the model were obtained by correlating the experimental data with the NRTL and UNIQUAC models. The relative root mean square error (RMSD) of the experimental value and the calculation formula was less than 0.79%, indicating that both the NRTL and UNIQUAC models can be well associated with experimental data.