The invention provides a ligustrazine substituted benzoic acid derivative with a general formula structure 1. The compound comprises a substituent group substituting a benzoic acid mother nucleus and containing a ligustrazine structure, the general structural formula is represented as the formula 1, wherein R1 is selected from any one of -H or 3,5,6-trimethyl ligustrazine-2-methylene; R2 is selected from any one of -H, -OH, 3,5,6-trimethyl ligustrazine-2-methyleneoxy or 3,5,6-trimethyl ligustrazine-2-formyloxy; R3 is selected from any one of -H, -OH, -OCH3, 3,5,6-trimethyl ligustrazine-2-methyleneoxy or 3,5,6-trimethyl ligustrazine-2-formyloxy; R4 is selected from any one of -H, -OH, 3,5,6-trimethyl ligustrazine-2-methyleneoxy or 3,5,6-trimethyl ligustrazine-2-formyloxy; at least one of R1-R4 is the substituent group containing the ligustrazine structure. The invention further provides a preparation method of the derivative and an application in preparation of drugs for treating brain nerve injury and sequelae of brain nerve injury.