5,11,17,23–5,11,17,23-Tetra-(tert-butyl)− 25,27-di-(2-aminomethyl pyridine acetamide)− 26,28-dihydroxy calix[4]arene (C4P2T) molecule was transferred to gold coated glass substrate for the first time as a sensor active layer for the detection of volatile organic compounds (VOCs) such as acetone, benzene, chloroform, ethyl acetate and methanol. UV–visible spectroscopy and surface plasmon resonance (SPR) techniques were employed to monitor Langmuir-Blodgett (LB) thin film layer during the fabrication process of each sensor layers. In order to determine film thickness and refractive index values of C4P2T LB film, SPR measurements were performed using a Kretschmann's prism configuration set-up system. Thickness and the refractive index values for the C4P2T LB thin films were determined to be 1.01 nm/layer and 1.59, respectively, by fitting the SPR curves using WINSPALL software based on the Fresnel formula. For the VOCs sensor application of the C4P2T LB thin film, reflected light intensity was recorded as a function of time by using SPR system. These measurements indicated that C4P2T LB thin film sensor layer was suitable for multiple usage with a fast response time (~ 3 s) and a recovery time (~ 3 s). The amount of C4P2T LB sensor responses against VOCs were followed by decreasing order acetone, chloroform, methanol, ethyl acetate and benzene. As a result, C4P2T LB film sensor has a sensitive and selective character and is suitable for VOCs sensor applications.