The hysteresis effect is a common problem in graphene field-effect transistors (FETs). Usually, the external doping to graphene is considered to be responsible for the hysteresis behavior, but is not yet clearly understood. By monitoring the doping of graphene and the hysteresis in graphene FETs under different atmospheres using in situ Raman spectroscopy, it is confirmed that the electrochemical doping of O2/H2O redox couple to graphene is responsible for the hysteresis effect. In addition, Raman spectra of graphene on SiO2 substrate show stronger doping than that suspended, which indicates that SiO2 substrate plays an important role in the doping of graphene. Herein it is proposed that the doping species (H2O and O2) are bounded at the interface of graphene/SiO2 substrate by hydrogen-bonds with the silanol groups on SiO2 substrate. The dynamic equilibrium process of the charge-transfer between H2O/O2 redox couple and graphene under electrical field modulation is carefully analyzed using Marcus–Gerischer theory. This work provides a clear view to the mechanism of the hysteresis effect, and is of benefit to a reliable design to suppress the hysteresis in graphene FETs.