Picoline amide-based calix[4]arene molecule was the first time deposited onto gold substrate as an active layer by using Langmuir-Blodgett (LB) coating technique. UV-visible, atomic force microscopy, and surface plasmon resonance (SPR) technique were used to control monolayer quality. The sensing properties were investigated by exposing the LB thin film to different percentage of organic VOCs vapors such as acetone, benzene, chloroform, ethyl acetate, and methanol in air-VOCs mixture. SPR results showed that this calix[4]arene molecule is a good candidate with a fast and reversible sensor response for VOCs sensing applications.