Cr-MOF nanoparticles were synthesized by a simple hydrothermal method, and their morphology and structure were characterized by SEM, TEM, and XRD techniques. The Cr-MOF modified glassy carbon electrode (Cr-MOF/GCE) was well constructed and served as an efficient electrochemical sensor for the detection of p-nitrophenol (p-NP). It was found that the Cr-MOF nanoparticles had significant electrocatalytic activity toward the reduction of p-NP. The Cr-MOF-based electrochemical sensor exhibited a low detection limit of 0.7 μM for p-NP in a wide range of 2~500 μM and could maintain excellent detection stability in a series of interfering media. The electrochemical sensor was also practically applied to detect p-NP in a local river and confirmed its validity, showing potential application prospects.