Tris(1,3-dichloro-2-propyl) phosphate (TDCIPP) has been consistently identified in various environmental media and biological specimens. The current understanding of the in vivo toxicities of TDCIPP remains limited, especially for its neurotoxicity and cognitive impairment effects. To better evaluate the potential damage of TDCIPP on learning and memory, Sprague Dawley (SD) Rats were subjected to TDCIPP exposure at doses of 40, 120, and 360 mg/kg/day for a duration of 90 days. Quantitative proteomic analysis, immunohistochemistry, and western blotting techniques were employed to assess alterations in proteins following exposure to TDCIPP. Open field test and Morris Water Mase tests were used to assess anxiety and spatial learning memory capacity in rats. In the present study, it was observed that the administration of TDCIPP induced anxiety and cognitive impairments in rats. Additionally, a noteworthy decrease in the number of neurons was observed in the hippocampal CA3 and DG regions. Subsequent bioinformati