Titanium dioxide (TiO₂) nanoparticles (NPs) are widely used in various applications due to their unique physicochemical properties compared to fine particles (FPs). This review highlights the current knowledge on the toxicology of TiO₂ NPs, focusing on their respiratory toxicity, translocation to systemic organs, and potential routes of human exposure. TiO₂ NPs can be inhaled, ingested, or come into contact with the skin, with inhalation being the primary route of exposure in workplaces. Studies have shown that TiO₂ NPs can cause significant pulmonary inflammation and damage, with nano TiO₂ being more potent than fine TiO₂ at the same mass burden. Translocation of TiO₂ NPs from the lungs to systemic organs, such as the liver, spleen, kidneys, and brain, has also been observed, although the rate of translocation is low. Oral exposure through food products containing TiO₂ NPs is another route of concern. Dermal exposure studies generally report that TiO₂ NPs do not penetrate the stratum corneum. Intravenous injection of TiO₂ NPs can lead to pathological lesions in various organs. The review also discusses the lack of epidemiological data on TiO₂ NPs despite their widespread use and production. Long-term inhalation studies in rats have reported lung tumors, emphasizing the need for further research on the carcinogenic potential of TiO₂ NPs. The review concludes by highlighting areas where more information is needed, such as the toxicokinetics and long-term health effects of TiO₂ NPs.Titanium dioxide (TiO₂) nanoparticles (NPs) are widely used in various applications due to their unique physicochemical properties compared to fine particles (FPs). This review highlights the current knowledge on the toxicology of TiO₂ NPs, focusing on their respiratory toxicity, translocation to systemic organs, and potential routes of human exposure. TiO₂ NPs can be inhaled, ingested, or come into contact with the skin, with inhalation being the primary route of exposure in workplaces. Studies have shown that TiO₂ NPs can cause significant pulmonary inflammation and damage, with nano TiO₂ being more potent than fine TiO₂ at the same mass burden. Translocation of TiO₂ NPs from the lungs to systemic organs, such as the liver, spleen, kidneys, and brain, has also been observed, although the rate of translocation is low. Oral exposure through food products containing TiO₂ NPs is another route of concern. Dermal exposure studies generally report that TiO₂ NPs do not penetrate the stratum corneum. Intravenous injection of TiO₂ NPs can lead to pathological lesions in various organs. The review also discusses the lack of epidemiological data on TiO₂ NPs despite their widespread use and production. Long-term inhalation studies in rats have reported lung tumors, emphasizing the need for further research on the carcinogenic potential of TiO₂ NPs. The review concludes by highlighting areas where more information is needed, such as the toxicokinetics and long-term health effects of TiO₂ NPs.