ABSTRACT Redox‐buffering systems in tumors heighten chemoresistance, yet most ROS‐responsive linkers used in prodrug design consume oxidants, exhibit limited sensitivity to endogenous ROS, and often require external triggers or complex formulations, constraining clinical translation. Here we report a phenylselanyl cyclohexenone self‐immolative linker that couples ROS‐triggered cleavage with organoselenium‐mediated redox amplification within a single small‐molecule architecture. Oxidation of the