Abstract: This study investigates the detection and optimization of 2-hydroxyterephthalic acid (HTA) formed from reactions of terephthalic acid (TA) with hydroxyl radicals (•OH) in liquid treated with a custom-built helium cold atmospheric plasma (CAP) jet. While •OH radicals in CAP have been widely studied in the gas phase, their cumulative presence and reactivity in liquid remain less explored. Here, TA is employed as a fluorescent dosimeter to quantitatively assess •OH dosing in liquid over a given treatment time. Three key operational parameters, helium flow rate, voltage amplitude, and frequency of the AC high-voltage sinusoidal supply, were systematically varied to determine optimal conditions for HTA formation. The highest HTA fluorescence was observed at 2 L/min, 4 kV, and 4 kHz, under which HTA formation exhibited a linear dependence on exposure time within 0–6 min. This linearity enables treatment time to serve as a reliable measure of •OH dosing, providing a practical calibration for controlled plasma–liquid interactions. Unlike prior studies focused on gas-phase optimization, this work emphasizes plasma–liquid systems, offering a quantitative framework to optimize •OH delivery for chemical, environmental, and biomedical applications.