<p>Organic hydroperoxides are a class of biologically significant molecules that exist ubiquitously in nature. The ideal synthesis is direct hydroperoxidation of C(sp³)–H bonds, which remained a substantial challenge, particularly for the unactivated C(sp³)–H bonds. Inspired by the bio-catalysis of cyclooxygenase, a direct and site-selective photochemical hydroperoxidation of unactivated C(sp³)–H bonds was thus developed involving O₂ as the oxidant and bromine radical as the catalyst. This method, demonstrated by plenty of substrates (63 examples) enables the late-stage functionalization of diverse types of natural products and/or drugs, such as terpenoids, amino acids, peptides, sugars and phosphonates.</p>