<p>2-Acetyl-6-methoxynaphthalene (2A6MN) is an important environmental transformation product of the anti-inflammatory drug naproxen (NPX), and causes accumulating concerns because of its undesired toxicity. Understanding the persistence and environmental fate of 2A6MN in natural and engineered systems is crucial for the ecological risk assessment of NPX transformation products. In this study, we systematically investigated the photochemical reactivity and behavior of 2A6MN under 254&#xa0;nm ultraviolet (UV₂₅₄) and natural sunlight irradiation. Our results indicated that 2A6MN exhibited strong absorption due to the conjugation between its carbonyl functionality and the naphthalene ring. Photolysis of 2A6MN was primarily driven by its triplet state, with quantum yields of 8.09 × 10⁻⁴ and 5.04 × 10⁻⁴ mol E⁻¹ under UV₂₅₄ and sunlight irradiation, respectively. The presence of dissolved oxygen significantly inhibited photolysis by quenching the triplet state. The photolysis pathways involved α-cleavage, dimerization, <i>O</i>-demethylation, and ring-opening. Some products generated by the photolysis of 2A6MN exhibited high ecotoxicity to aquatic organisms, potentially threatening the aquatic environment and public health. Dissolved organic matter (DOM) exhibited inhibitory effects on 2A6MN photolysis, possibly by screening light and quenching its triplet. GCSOLAR predicted that the direct photolysis of 2A6MN in natural surface water diminished remarkably with increasing water depth due to the attenuation of incident radiation. The photolysis half-lives of 2A6MN at a depth of 5&#xa0;m were approximately 20-times higher than those of the near surface. Results of this study fulfills the knowledge gaps in the photochemical reactivity and environmental fate of NPX transformation products in UV-irradiated wastewater and sunlit surface waters. </p> Graphical abstract <p></p>