The bioavailability and toxicity of organic pollutants in aquatic organisms can be largely affected by the co-existed nanoparticles. However, the impacts of such combined exposure on the visual system remain largely unknown. Here, we systematically investigated the visual toxicity in zebrafish larvae after single or joint exposure to titanium dioxide nanoparticles (n-TiO2) and bis(2-ethylhexyl)-2,3,4,5-tetrabromophthalate (TBPH) at environmentally relevant levels. Molecular dynamics simulations revealed the enhanced transmembrane capability of the complex than the individual, which accounted for the increased bioavailability of both TBPH and n-TiO2 when combined exposure to zebrafish. Transcriptome analysis showed that co-exposure to n-TiO2 and TBPH interfered with molecular pathways related to eye lens structure and sensory perception of zebrafish. Particularly, n-TiO2 or TBPH significantly suppressed the expression of βB1-crystallin and rhodopsin in zebrafish retina and lens, which was further enhanced after co-exposure. Moreover, we detected disorganized retinal histology, stunted lens development and significant visual behavioral changes of zebrafish under co-exposure condition. The overall results suggest that combined exposure to water borne n-TiO2 and TBPH increased their bioavailability, resulted in severer damage to optic nerve development and ultimately abnormal visual behavior patterns, highlighting the higher potential health risks of co-exposure to aquatic vertebrates. ENVIRONMENTAL IMPLICATION: Titanium dioxide nanoparticles (n-TiO2) is able to interact with bis(2-ethylhexyl)-2,3,4,5-tetrabromophthalate (TBPH) in aquatic environments, but their combined harms and impacts on the visual system of fish are still unclear. The present study discovered that n-TiO2 with TBPH induced stronger membrane damage than individual n-TiO2 through molecular dynamics simulation, then leaded to higher bioavailability of both two in zebrafish under combined exposure. In addition, this study firstly found visual toxicity of environmental dose of n-TiO2 exposure on zebrafish at early developmental stage, and these adverse effects were significantly enhanced when combined exposure to n-TiO2 and TBPH.