The acute toxicity (-log EC50) to Photobacterium phosphoreum and the n-octanol/water partition coefficient (log Kow) of 31 kinds of substituted thiophenols were determined at 298.15K. The -log EC50 values of studied chemicals are between 4.26 and 5.89. Their log Kow values are between 1.34 and 4.02. Comparative molecular field (CoMFA) and comparative molecular similarity index analysis (CoMSIA) models established were successful in predicting -log EC50 and log Kow values of halogenated, methylic, amino and methoxy thiophenols. The size of molecule is the main factor influencing the properties. No correlation was found between the properties and their structural and thermodynamic descriptors from DFT calculation.