3-Nitrotyrosine (3-NT), an oxidative stress biomarker, is closely associated with various diseases. Thus, rapid and sensitive detection of 3-NT is of great significance for preventing and treating diseases. Herein, we reported a new 3D zinc-based metal-organic framework (Zn-MOF) [Zn(L)(HBTC)] (L = (E)-4,4'-(ethene-1,2-diyl)bis[(N-pyridin-3-yl)benzamide], H3BTC = 1,3,5-benzenetricarboxylic acid), which was structurally characterized by single crystal X-ray diffraction, IR, PXRD and TG. The Zn-MOF can be used as a highly efficient fluorescence sensing material to provide a direct and low-cost method for the rapid detection of 3-NT and shows high sensitivity with a KSV value of 6.596 × 104 M-1, a rapid luminescence response within 24 s, excellent selectivity, high anti-interference ability and good recyclability. It is the first example of a MOF being used to directly detect 3-NT as a luminescence sensor to our knowledge. The sensing mechanism of the Zn-MOF towards 3-NT is discussed in detail, which provides a basis for the rational design of MOF sensing materials and their application in biomarker detection.