AbstractTitanium dioxide (TiO₂) is a common additive that is increasingly used in consumer products, food, pharmaceutical dosage forms and cosmetic articles. However, due to size reduction of TiO₂ particles from the microscale to the nanoscale, application areas of this material are expanding, especially in the food sector, which makes investigations of nano-TiO₂ crucial. This review focuses on two important topics of current research regarding the oral pathway: 1) anatomy of the orogastrointestinal tract, composition of epithelial and mucus layer, and pH changes; 2) cell entry mechanisms, cytotoxicity and translocation. Sufficient knowledge on the oral uptake route is not yet available but is highly needed for human risk evaluation.