Abstract: Xanthones and their derivatives have been reported to exhibit inhibitory activities towards Plasmodium falciparum. In order to provide deep insight into the correlation between inhibitory activities and structures of xanthones, linear regression method was employed to establish QSAR models for 16 xanthones derivatives with different structure. The accuracy and predictive power of the proposed QSAR model were verified, optimized, and validated by semi empiric PM3 method. The result of this research showed that the best QSAR model was model 3.