The toxic impact of titanium dioxide nanoparticles (TiO₂NPs) on human health is of prime importance owing to their wide uses in many commercial industries. In the present study, the effect of different doses and exposure time durations of TiO₂NPs (21nm) inducing oxidative stress, biochemical disturbance, histological alteration and cytogenetic aberration in mice liver and bone marrow was investigated. Different doses of (TiO₂NPs) (50, 250 and 500mg/kg body weight) were each daily intrapertioneally injected to mice for 7, 14 and 45days. Aspartate and alanine aminotransferases (AST &ALT), gamma glutamyl transpeptidase (GGT), total protein, total antioxidant capacity (TAC), malondialdehyde (MDA), glutathione (GSH), catalase (CAT) and nitric oxide (NO) levels were measured. The work was extended to evaluate the liver histopathological pattern and the chromosomal aberration in mice spinal cord bone marrow. The results revealed severe TiO₂NPs toxicity in a dose and time dependent manner with positive correlation (r=0.98) for most investigated biochemical parameters. The same observation was noticed for the histological analysis. In case of cytogenetic study, chromosomal aberrations were demonstrated after injection of TiO₂NPs with 500mg/kg b. wt. for 45days. In conclusion, the selected biochemical parameters and the liver architectures were influenced with dose and time of TiO₂NPs toxicity, while the genetic disturbance started at the high dose of exposure and for long duration. Further studies are needed to fulfil the effect of TiO₂NPs on pharmaceutical and nutritional applications.