QSAR analysis of indanone and aurone derivatives as AChE inhibitor has been performed using various physicochemical parameters on Chem- Office software. Energy minimization was carried out using molecular mechanics (MM2) force field and MOPAC. The biological activity data were taken as negative logarithmic dose in moles (pIC50) for QSAR analysis. Sequential multiple linear regression method was used to develop relationship between inhibitory activity and physicochemical parameters, employing VALSTAT. The series was divided into a training set of 23 compounds and test set of 9 compounds. Several equations were obtained, the statistically significant equation was considered as best model. LUMO (Lowest Unoccupied Molecular Orbital) energy, Diameter and Gibbs Free Energy (G) contributes the equation. The model has correlation coefficient (r) of 0.873. The equation shows significance level more than 95% against tabulated value F=8.53, with a low standard deviation of estimation demonstrate accuracy of the model.