Herein, mechanistic aspects of the photogeneration and quenching of guanine radical cation through one-electron oxidation of the G-quadruplex of G2T2G2TGTG2T2G2 (TBA) sequence were investigated by a combined quantum mechanical/molecular mechanical (QM/MM) approach at the CASPT2//CASSCF/AMBER level of theory. Herein, one electron promotion of the oxygen lone pair of the photo-excited photosensitizer peroxydisulfate to its O-O σ* orbital was first demonstrated to become tunable through the varied reduction ability of the G base in the presence or absence of interbase hydrogen bonding, thereby dynamically controlling the deprotonation site in G-quadruplex TBA. The quenching of G radical cation mediated by the formation of SO42-via photoinduced electron transfer can be triggered effectively by the deprotonation reaction of free proton rather than that of the hydrogen-bonded proton in G-G (G-quartet) and G-T (loop) aqueous surrounding. By calculating the deprotonation paths for the G radical cation, the deprotonation reactions in G-quadruplex TBA were verified to proceed predominantly along the site of imino proton (N1-H) in the loop moiety; this showed the coexisting occurrence of amino (N2-H) deprotonation in the G-quartet part. The mechanistic features discussed in this study represent significant advances in the understanding of DNA radical chemistry.