Psychotic symptoms have been widely spread and several drugs have been proposed to suppress its consequences including trifluoperazine (TFP). Here we introduce an electrochemical sensor based on glassy carbon electrode modified with a composite of hematite nanoparticles (FeNPs)/ionic liquid crystal (ILC)/graphene (RGO) for simple and direct determination of TFP. The sensor proved to be highly effective and sensitive due to the synergistic effects of FeNPs, ILC and RGO. The electrocatalytic oxidation of TFP was investigated by cyclic voltammetry (CV) and differential pulse voltammetry (DPV). Surface morphology was examined by scanning electron microscopy (SEM). Various figures of merit were evaluated including effects of pH and scan rates on the voltammetric response of TFP. Under optimal operational conditions, linear response was in the concentration range of 9 x 10(-10) to 1 x 10(-7) mol L-1 and 2 x 10(-6) to 2 x 10(-4) mol L-1 for TFP with correlation coefficients 0.997 and 0.998, respectively. The lower limits of detection and quantification were 2.29 x 10(-12) mol L-1 and 7.65 x 10(-12) mol L-1, respectively. The sensor showed good stability, reproducibility, repeatability, anti-interference ability and selectivity. It was possible to determine TFP in real human samples and pharmaceutical formulations. (C) 2016 The Electrochemical Society. All rights reserved.