The invention discloses a preparation method of diethyl ethylisopentylmalonate. The preparation method comprises following steps: 1), ethanol and sodium react to generate sodium ethoxide; 2), diethyl ethylmalonate is added to sodium ethoxide obtained in the step 1), and diethyl ethylmalonate sodium salt is generated; 3), 1-bromo-3-methylbutane is added to the diethyl ethylmalonate sodium salt obtained in the step 2), and diethyl ethylisopentylmalonate is generated after reaction. Diethyl ethylisopentylmalonate is prepared from ethanol, sodium, diethyl ethylmalonate and 1-bromo-3-methylbutane as the raw materials, and prepared diethyl ethylisopentylmalonate has high yield and high purity and meets the drug quality standard.