A novel colorimetric and fluorescent “switch-on” probe based on xanthene-triphenylamine was developed for detection of Hg2+, which threatens public health, food safety and the environment. The probe displayed superior colorimetric and fluorescent selectivity/sensitivity toward Hg2+ over a series of metal ions via Hg2+-triggered deprotection reaction. Hg2+ induced a ∼18-fold enhancement in emission intensity of probe TXS with yellow fluorescence (λem = 558 nm) and led to distinct color transition from light yellow to blue or yellow under daylight depending on solvent mixture. Detection parameters were optimized and examined for the influence that they exerted on the detection which involved the usage of the Box-Behnken design methodology. The sensing pathway was also examined theoretically by DFT and TD-DFT calculations. The probe was successfully utilized for the detection of Hg2+ in several food and water samples with good recoveries. Cell imaging studies demonstrated that the probe was suitable for Hg2+ detection in live cells.