We report a new design of photolabile acetal-containing amphiphilic block copolymers. Acetals as protecting groups for carbonyls or diols can be hydrolyzed under acidic condition but very stable with respect to hydrolysis at pH>7. When combining light-capturing chromophores with acetals, the hydrolysis of acetals can be activated by light to design dual responsive acetal-containing polymers. Using acetalization reaction of 2,3-dihydroxypropyl methacrylate with benzaldehyde derivatives, two new acetal-containing photolyzable monomers have been designed. Comparable to commonly used photolabile monomers containing nitrobenzyl esters, the two acetal-containing monomers are easy to polymerize using atom transfer radical polymerization with excellent molecular weight and dispersity control. We studied the cleavage kinetics and mechanism of acetal groups in both monomers and polyethylene oxide (PEO)-containing amphiphilic block copolymers using H-1 NMR and UV-vis spectroscopy. o-Nitrobenzaldehyde acetal showed a Norrish Type II rearrangement to form benzoic ester; while, 2,5-dimethoxy benzaldehyde acetal was photolabile to completely release 2,3-dihydroxypropyl methacrylate. The photocleavage of acetals is a zero-order reaction in regardless of molecular states of acetals; while, the acid-cleavage of acetals proves to be a first-order kinetics and the cleavage becomes much slower for polymers. The self-assembly of acetal-containing amphiphilic block copolymers and the acid-/light-controlled dissociation of their vesicles have been investigated. We demonstrate that those acetal-containing polymers are potentially useful as smart drug delivery systems where the release kinetics of payloads is tunable using light and pH as triggers. (C) 2018 Wiley Periodicals, Inc.