The effect of various concentrations (1.9–38.8 mg/l) of oil products (diesel fuel) on the activity of lysosomal deoxyribonuclease in White Sea mussels Mytilus edulis L. were studied in aquarium experiments. The most significant changes in the activity and range of DNase isoforms occurred in soft tissues under the impact of low (1.9 mg/l) and medium (8.4 & 17.4 mg/l) doses of diesel fuel. When the concentrations of petroleum hydrocarbons were high (38.8 mg/l) differences in the nuclease activity and the fractional composition of the enzyme between the treatment and the control were minor. We discuss the potential mechanisms behind the high resistance of the mussels to oil pollution, and the role of nucleases in the selected biochemical adaptation strategies, which differ in the involvement of the genome in the compensatory adjustments of the metabolism in response to different doses of the pollutant.