In this work, a graphene oxide (GRO)-based temperature-sensitive smart catalytic support material was developed by tethering biodegradable and hydrophilic poly(N-vinylcaprolactam) (PVCL) on a GRO (i.e., GRO-PVCL) surface. GRO-PVCL-supported palladium catalyst (i.e., Pd/GRO-PVCL) was then prepared for tizanidine (TZN) electroreduction. The impact of a temperature-sensitive smart surface on the electrochemical and electrocatalytic properties was examined. Moreover, when the large surface area, excellent electron transfer, and electrochemical catalysis abilities of GRO were combined with the responsive characteristics of PVCL, temperature-triggered reversible electrocatalysis of TZN with enhanced sensitivity has been proved. Results designated that GRO- PVCL exposed the hydrophilic surface at 20 degrees C, resulting in Pd NPs highly dispersed on the GRO-PVCL surface. Subsequently, the wettability of the Pd catalyst surface arbitrarily adapted to hydrophobicity at 40 degrees C, which highly enhanced the TZN reduction on the catalyst in electrochemical detection. The synergistic effect amid Pd and GRO-PVCL on Pd/GRO-PVCL improved the electrocatalytic activity of TZN. The detection of TZN with the Pd/GRO-PVCL modified electrode ranged from 0.02 to 276 mu M with a low detection limit of 0.0015 mu M at 40 degrees C. The Pd/GRO-PVCL modified electrode also possesses excellent stability, reproducibility, and anti-interference ability. Lastly, the modified electrode attained good recovery results in human urine and human plasma samples for the determination of TZN and also pharmacokinetics study in rat plasma.