The invention discloses a derivative of RVX-208 based on a BRD4 inhibitor as well as a preparation method and application of the derivative. The structure of the derivative is shown in formula I. Thepreparation method comprises the following steps: ensuring that a compound shown in formula 8 and a compound shown in formula 9 react, so as to obtain a compound shown in formula 10; ensuring that thecompound shown in formula 10 reacts with malonic acid, succinic acid or glutaric acid, and then reacts with ethylene carbonate, 2-halogenated isobutyric acid or 4-halogenated phenoxy isobutyric acid;or ensuring that the compound shown in formula 10 directly reacts with ethylene carbonate, 2-halogenated isobutyric acid or 4-halogenated phenoxy isobutyric acid. The invention further provides the application of the derivative. The derivative can improve the activity for reducing cholesterol or reduce the level of cholesterol and triglyceride at the same time.