Ecologic and health effects of applying materials with advanced functions for leather surface finishing are priorities for the European leather industry and contribute to the increase of added value and durability of leather and fur articles. The innovative properties of Ag/TiO2 nanomaterials (NMs) on leather surface are due to their antimicrobial, self-cleaning and flame retardant characteristics. The NANO_SAFE_LEATHER project aims to contribute to the industrial development of safer and advanced leathers that make use of Ag/TiO2NMs, which are ecological alternatives to volatile organic biocides, organic solvents and halogenated flame retardants. The cytotoxicity study of the Ag/TiO2NM's efficiency for leather functionalization related to the dose response on human health is very important for their large scale application in footwear industry. The paper presents the strategy of research regarding the leather surface finishing by spraying and by physical deposition of Ag/TiO2NMs, the impact of NMs use in industrial environment and in connection with wearing behavior. In vitro assay to study the cytotoxicity of the Ag/TiO2NMs, leather functionalized with Ag/TiO2NMs and leached Ag/TiO2NMs on different human cells, the cell morphology and cell death mechanism as well as the exposure risk assessment on lung cells will allow to estimate for the first time the impact of NMs industrial application in leather and footwear industry and on consumer health. In silico study of human cells in vitro interacted with Ag/TiO2NMs provides information on the potential changes induced by the NPs on cellular morphology and helps build a domain ontology.