Phenolic compounds are common water pollutants and include a wide variety of organic chemicals. The effects of three sublethal concentrations of phenol on liver histology and some biochemical parameters of Oncorhynchus mykiss after 8 weeks exposure were investigated in this study. A total of 80 rainbow trout (O. mykiss) were randomly divided into four groups (n ¼ 20). Control group was kept in water without any add-on material, while experimental groups were exposed to the concentration of 0.6, 1.2 and 2.4 mg/L of phenol solution. At the end of the study period, the weight of liver, condition factor (CF) and hepatosomatic index (HSI) were measured. Tissue and blood samples were taken separately for histologic evaluation and serum biochemical parameters assay, respectively. In fish treated with phenol, significant reduction in liver weight, CF, HSI ratio, diameter of hepatocytes and hepatocytes nuclear diameter (p < 0.05) was recorded. Total protein and albumin decreased significantly in treated fish in comparison with control (p < 0.05), but levels of cholesterol, glucose, alkaline phosphatase, lactate dehydrogenase, aspartate aminotransferase and alanine aminotransferase in fish exposed to different concentrations of phenol showed a significant increase (p < 0.05). These findings showed that phenol could cause its harmful impacts even in very low concentrations.