The photo-regulation of transgene expression is one effective approach in mammalian synthetic biology due to its high spatial and temporal resolution. While DNAs are mainly used as vectors, modified RNAs (modRNAs) are also useful for medical applications of synthetic biology, because they can avoid insertional mutagenesis and immunogenicity. However, the optogenetic control of modRNA-delivered transgenes is much more difficult than that of DNA-delivered transgenes. Here, we develop two types of photo-controllable translational activation systems that are compatible with modRNAs. One is composed of a heterodimerization domain-fused split translational activator protein and a photocaged heterodimerizer. The other is composed of a destabilizing domain-fused translational activator protein and a photocaged stabilizer. The destabilized type can be used for not only translational activation but also translational repression of the modRNAs. These photo-controllable translation systems will expand the application of mammalian synthetic biology research. Display omitted •Two photo-controllable translational activators for synthetic mRNAs are developed•One is a split translational activator that is reconstituted by light•The other is a destabilized translational activator that is stabilized by light•The destabilized type enables both translational activation and repression Nakanishi et al. develop photo-controllable translational regulation systems for synthetic mRNAs containing modified nucleosides. These systems are composed of photocaged ligands, ligand-responsive domain-fused translational regulatory proteins, and target synthetic mRNAs containing a protein binding motif. They enable light-inducible translational activation or repression of the target mRNAs in mammalian cells.