We identified peroxiredoxin-4 (Prx-4) as a protein interacting with the β isoform of the thromboxane A2 receptor (TPβ) by yeast two-hybrid analysis. Prx-4 co-immunoprecipitated constitutively with TPβ in HEK293 cells. The second and third intracellular loops as well as the C-terminus of TPβ interacted directly with Prx-4. Co-expression of Prx-4 caused a 60%decrease in cell surface expression of TPβ. Prx-4 and TPβ predominantly co-localized in the endoplasmic reticulum. Co-expression of Prx-4 in cells treated with H2O2 targeted TPβ for degradation. We show for the first time an interaction between a receptor involved in oxidative stress and Prx-4, an anti-oxidative enzyme.