The fluorometric measurement of an individual reactive oxygen species (ROS) provides useful biological and biochemical information on ROS as important mediators for the pathological conditions of various diseases and yet requires a highly specific probe toward the target ROS. To design such a specific ROS probe, this report proposes a new strategy based on protection-deprotection chemistry between fluoresceins and their derivatives protected with benzenesulfonyl groups. The strategy has allowed developing new fluorescent probes toward extra- and intracellular hydrogen peroxide or superoxide. Herein, I outline the strategy used for the design of these ROS probes and their probe performance with high selectivity toward hydrogen peroxide and superoxide, which could not be achieved until a simple deprotection, namely, a nonredox reaction, was used as a fluorescing process.