The surface modification of Poly (acrylamide-co-methylenbisacrylamide-co-N-(4-(2-(phenylcarbamothioyl)hydrazineyl)phenyl)methacrylamide) as a sensor (AR) via titanium dioxide as a novel colorimetric nanocomposite sensor with high sensitivity and selectivity for determination of fluoride anion was described. The colorimetric response of the AR has been screened in dimethyl sulfoxide /Water with a volumetric ratio of 7:3 and acetonitrile in separate media with equal amounts of various anions. In the presence of the mentioned anionic solutions, only the solutions containing fluoride ions, made a significant change in color from pale yellow to orange-red via the –NH deprotonation mechanism, which could be detected with the naked eye. The Box-Behnken design, response surface methodology through UV-Vis spectroscopy techniques in various pH and temperatures and reaction times were tested to optimize the AR conditions. Also, a lateral flow assay test of the synthesized AR detected fluoride ions in real-life samples, including water, contrary to different sources such as toothpaste and mouthwash. Furthermore, according to the World Health Organization report on fluoride ion toxicity in water, the detection limit of the AR was lower than of the declared level.