The recent discovery of dihydrothiophenone derivatives as P. falciparum dihydroorotate dehydrogenase (PfDHODH) inhibitors spurs quantitative examination of the relationship between the properties of these compounds and the observed antimalarial activity. Quantitative Structure-Activity Relationship (QSAR) study was carried out on dihydrothiophenones as inhibitors of PfDHODH in PfDd2 strain using multilinear regression analysis.The inhibitory activity was shown to be a function of eight DRAGON-type descriptors, namely, HATS7p, Hy, Mor17e, RDF145m, G1u, HATS8v, H5e, and Mor22m.The model indicates that an electronically dense molecule with highly electronegative atoms and less number of hydrophilic groups tend to be a potentantiplasmodial agent.