Quantitative structure toxicity relationship (QSTR) equations were obtained to predict and describe the cytotoxicity of 31 phenols using log LD 50 as a concentration to induce 50% cytotoxicity of isolated rat hepatocytes in 2 h and log P as octanol/water partitioning: log LD 50 (μM)=−0.588(±0.059)log P+4.652(±0.153) ( n=27, r 2=0.801, s=0.261, P<1×10 −9). Hydroquinone, catechol, 4-nitrophenol, and 2,4-dinitrophenol were outliers for this equation. When the ionization constant p K a was considered as a contributing factor a two-parameter QSTR equation was derived: log LD 50 (μM)=−0.595(±0.051)log P+0.197(±0.029)p K a+2.665(±0.281) ( n=28, r 2=0.859, s=0.218, P<1×10 −6). Using σ +, the Brown variation of the Hammet electronic constant, as a contributing parameter, the cytotoxicity of phenols towards hepatocytes were defined by log LD 50 (μM)=−0.594(±0.052)log P−0.552(±0.085) σ ++4.540(±0.132) ( n=28, r 2=0.853, s=0.223, P<1×10 −6). Replacing σ + with the homolytic bond dissociation energy (BDE) for (X-PhOH+PhO →X-PhO +PhOH) led to log LD 50 (μM)=−0.601(±0.066)log P−0.040(±0.018)BDE+4.611(±0.166) ( n=23, r 2=0.827, s=0.223, P<0.05). Hydroquinone, catechol and 2-nitrophenol were outliers for the above equations. Using redox potential and log P led to a new correlation: log LD 50 (μM)=−0.529(±0.135)log P+2.077(±0.892) E p/2+2.806(±0.592) ( n=15, r 2=0.561, s=0.383, P<0.05) with 4-nitrophenol as an outlier. Our findings indicate that phenols with higher lipophilicity, BDE, or σ + values or with lower p K a and redox potential were more toxic towards hepatocytes. We also showed that a collapse of hepatocyte mitochondrial membrane potential preceded the cytotoxicity of most phenols. Our study indicates that one or a combination of mechanisms; i.e. mitochondrial uncoupling, phenoxy radicals, or phenol metabolism to quinone methides and quinones, contribute to phenol cytotoxicity towards hepatocytes depending on the phenol chemical structure.