The application of titanium dioxide (TiO2) nanoparticles (NPs) in the manufacturing of consumer products has increased tremendously and with the potential to induce deleterious effects on aquatic biota. There have been reports on metal oxide NP toxicity in aquatic organisms, however, information on cytotoxicity and genotoxicity of TiO2 NPs on the African catfish, Clarias gariepinus, is scarce. In this study, we investigated the genotoxicity and haematotoxicity of TiO2 NPs in C. gariepinus using the micronucleus (MN) assay and haematological analysis, respectively. Juvenile C. gariepinus were exposed to 6.25, 12.5, 25.0, 50.0 and 100.0 mg L−1 concentrations of TiO2 NPs for 7 and 28 days. Benzene (0.05 mL L−1) and dechlorinated tap water were used as positive and negative controls, respectively. Data of the MN showed a significant ( p < 0.05) concentration-dependent increase in the frequency of MN at both exposure periods in comparison to negative control. Red blood cells, haematocrit, platelets and heterophils significantly reduced with an increased mean corpuscular haemoglobin concentration and lymphocytes at the 7-day exposure period, while in the 28-day exposure period, mean cell volume, mean corpuscular haemoglobin and lymphocytes had a significant increase in comparison with the negative control. This study indicates that TiO2 NPs induced cytogenetic and haematological alterations in C. gariepinus and is of relevance in biodiversity and aquatic health management.