A novel electrochemical sensor based on poly-(diallyldimethylammonium chloride) (PDDA), gold nanoparticles (AuNPs) and multi-walled carbon nanotubes (MWCNTs) modified organic electrochemical transistors (OECTs) was successfully fabricated and applied to determination of Tyrosine (Tyr). The as-prepared device was characterized by field emission scanning electron microscopy (FE-SEM) and electrochemical workstation. Electrochemical performance of the modified OECT for detection of Tyr was investigated by cyclic voltammetry (CV) and chronoamperometry methods. Compared with the OECTs with the bare and the MWCNTs/PDDA modified OECTs Au gate electrode, the ultimate OECT with the MWCNTs/PDDA/AuNPs modified Au gate electrode displayed higher catalytic activity toward the oxidation of Tyr. The MWCNTs/PDDA/AuNPs modified OECT exhibited a linear response to Tyr over a wide concentration range of 03 mu M to 10 mu M with a detection limit of 10 nM in PBS solution (pH = 7.4), suitable for Tyr detection in human body fluids. Considering the main advantages of OECT such as low cost, no need for pre-treatment, easy to use and real-time detecting capability, we believe that the MWCNTs/PDDA/AuNPs modified OECT can potentially be employed as a highly-sensitive, real-time, portable and disposable sensor for practical detection of Tyr in real sample.