A screen-printed electrochemical sensor based on Fe3O4@cellulose nanocrystals/Cu nanocomposite (Fe3O4@CNC/Cu) has been constructed for the sensitive detection of venlafaxine. The magnetic Fe3O4@cellulose nanocrystal/Cu nanocomposite was prepared by a green procedure using a plant extract (Petasites hybridus leaf) as a stabilizing and reducing agent for copper. The formation of Fe3O4@CNC/Cu was validated through X-ray diffraction, Fourier transform infrared spectroscopy, transmission electron microscopy, field emission scanning electron microscopy, energy-dispersive X-ray spectroscopy, ultraviolet-visible spectral analysis, vibrating sample magnetometer, and thermal analysis. Fe3O4@CNC/Cu was next used for modifying a graphite screen-printed electrode, intended for the analysis of venlafaxine concentration. The electrochemical behavior of venlafaxine on the resulting electrode was evaluated through cyclic and differential pulse voltammetry and chronoamperometry. The tests indicated that the sensor has good performance for the electrochemical detection of venlafaxine. Under optimized conditions, the linear dynamic range for venlafaxine concentrations by the modified electrode was 0.05-600.0 mu M, and the limit of detection was 0.01 mu M. In addition, the developed technique was also demonstrated as a selective, easy, and precise sensor to identify venlafaxine in urine, water, and pharmaceutical formulation samples.