The study of the DNA damage response in erythrocytes after exposure to volatile organic compounds (VOCs) can present evidence for its potential effect as genotoxic- biomarkers for environmental pollution. Although VOCs are dangerous pollutants, still little is known about hemotoxic, cytotoxic, and genotoxic effects of such pollutants on fish. We optimized an assay method for apoptosis and DNA damage in erythrocytes of adult tilapia fish after 15 days exposure to benzene (0.762 ng/L), toluene (26.614 ng/L), and xylene (89.403 ng/L). The highest level of apoptosis and DNA damage were recorded in benzene-exposed fish, as was the highest level of histopathological alterations in gills, liver, and kidney. The imbalance of the antioxidants profile explained the stress-case reported in exposed fish. These results suggest that hemotoxic, cytotoxic, genotoxic, and tissue damage were recorded after exposure to BTX in Oreochromis niloticus.