The electrocatalytic oxidation of venlafaxine (VEN) was investigated at a glassy carbon electrode (GCE), the modified electrode by a gel containing multiwall carbon nanotubes (MWCNTs) and a room-temperature ionic liquid (RTIL), 1-butyl-3-methylimidazolium hexafluorophate (BMIMPF6) in 0.10 mol L−1 phosphate buffer solution (PBS, pH 6.8). It was found that an irreversible anodic oxidation peak of VEN with the peak potential (Epa) as 0.780 V appeared at MWCNTs-RTIL/GCE. The electrode reaction process was a diffusion-controlled one and the electrochemical oxidation involved two electrons transferring and two protons participation. Furthermore, the charge-transfer coefficient (α), and the electrode reaction rate constant (kf) of VEN were found to be 0.91 and 3.04×10−2 s−1, respectively. Under the optimized conditions, the electrocatalytic oxidation peak currents were linearly dependent on the concentration of VEN in the concentration range from 2.0×10−6 mol L−1 ~ 2.0×10−3 mol L−1 with the limit of detection (S / N = 3) as 1.69×10−6 mol L−1. The proposed method has been successfully applied in the electrochemical quantitative determination of VEN content in commercial venlafaxine hydrochloride capsules and the determination results could meet the requirement of the quantitative determination.