Extensive use of nanotechnology in multiple commodities is raising concern about nanotoxicity and particularly. Particularly, many studies reported the health hazardous effects of titanium dioxide nanoparticles (TiO2-NPs). Study focuses on toxicity and accumulation of TiO2-NPs in tilapia (Oreochromis mossambicus). For this purpose, Tilapia were kept in water tanks, acclimatized for fourteen days, and treated with different doses of TiO2 nanoparticles 0, 0.5, 1.0, and 1.5 mg TiO2-NPs /L. Results revealed an increase in accumulation of TiO2-NPs with an increase in doses. Moreover, with higher dose (1.5 mg /L) gills had maximum levels compared to muscles and liver tissues whereas other doses showed different accumulation patterns. A significantly higher concentration of catalase, glutathione, and lipid peroxidation was recorded in gills (p < 0.05) and superoxide dismutase in the liver. Characteristics like thickening and fusion in lamellae, rupturing of filaments and hyperplasia of gills were also recorded. The phenomenon of increased necrosis and apoptosis in the liver was also noticed with increasing concentration of TiO2-NPs along with formation of sinusoid spaces and condensed nuclear bodies. Elevated values of olive tail movement and % tail DNA were also noticed with increased concentration of TiO2-NPs. This study concluded that TiO2-NPs produced oxidative stress by accumulation in soft tissues and induced pathology and genotoxicity.