Ferricyanide-promoted oxidative activation of N-acylated ?-aminothioacids for amide bond formation with ?-aminonitriles was recently shown to be a plausible pathway for prebiotic peptide synthesis. Here we described the finding that by adding sodium azide and thiols, ferricyanide oxidation can elicit highly efficient and clean conversion of fully unprotected peptide or protein thioacids in neutral aqueous media to the corresponding thioesters. This transformation enables the development of ferricyanide-promoted thioacidbased native chemical ligation as a new redox-based method for chemical protein synthesis, which does not need to change pH and is therefore, operationally easy for ligation at small scales. The effectiveness of the ferricyanide-promoted thioacid-based native chemical ligation was illustrated by synthesis of an ISG15-modified MDA5 segment under nondenaturing conditions and synthesis of an acetylated ubiquitin-modified histone H2A through an N-to-C sequential ligation. This work broadens the concept of on-demand oxidative activation strategy for protein ligation and provides a new useful supplement to the repertoire of methods for chemical protein synthesis, particularly for the studies on proteins carrying ubiquitin family modifications.